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Nucleocapsid Protein Chaperoning of Nucleic Acids at the Heart of HIV Structure, Assembly and cDNA Synthesis

Jean-Luc Darlix1, Marcelo Lopez Lastra2, Yves Mély3, Bernard Roques4.

1 LaboRetro, Unité de Virologie Humaine, INSERM #412 ENS de Lyon, 46 allée d'Italie, 69364 Lyon, France.

2 Biochemistry Department, McIntyre Medical Sciences Bldg., McGill University, 3655 Promenade Sir William Osler, H3G1 Y6, Montreal, Canada.

3 Laboratoire de Pharmacologie et Physicochimie des interactions cellulaires et moléculaires, UMR 7034 du CNRS, Faculté de Pharmacie, Université Louis Pasteur, 74 route du Rhin, 67401 Illkirch, France.

4 Département de Pharmacochimie Moléculaire et Structurale, INSERM #266, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 Paris, France.


The dawn of Nucleocapsid protein

Throughout the twentieth century, retroviruses led the way to remarkable discoveries fundamental to our understanding of life. The study of retroviruses has triggered exciting findings such as that of oncogenes and their implication in cancer (30,35,104,116) and the role of reverse transcribed elements in the plasticity of eukaryotic genomes (11,92,105), to name just two. The knowledge generated from the study of retroviruses has been paramount in bio-medicine and pivotal in the development of now commonplace techniques and applications such as molecular cloning, gene therapy, and novel diagnostics for cancer and viral infections. Bio-technology has come a long way since the first descriptions of oncoretroviruses (77,189), their visualization by electron microscopy (16) and the identification of the viral DNA polymerase, the celebrated reverse transcriptase (RT) (11, 204), and a small oncoviral nucleoprotein named the nucleocapsid protein (NC).

The NC story began with the isolation of ribonucleoprotein structures from oncoviruses (63,64,192) that supported cDNA synthesis (43). NC was found to be a nucleic acid binding protein with preferential binding to the dimeric 70S genomic RNA (63,64,83,159,176,193,198). In those early days not only did NC receive little attention, but results on NC-RNA interactions and NC specific binding sites on the genomic RNA of oncoretroviruses were obscured by the misidentification of the matrix protein as the specific partner of the 70S RNA (57,194; corrected in 147). In summary, data indicate that NC has a strong preference for single stranded regions flanking or within structured RNA domains and tightly binds to a small number of genomic RNA sequences rich in U and Gs, mostly located in the 5' leader domain (147,194). Later, two series of observations dramatically enhanced our understanding of NC properties and functions, effectively kick-starting the NC story. Firstly, NC was found to be the driving force in genomic RNA dimerization and packaging into assembling RSV and MuLV virions (97,148,149). Secondly, NC was shown to chaperone viral RNA dimerization in vitro and primer tRNA annealing to the primer binding site (PBS) in MuLV and RSV (171,172) (for HIV-1 see refs. 13,40,41,69,82,106) . Data also suggested that NC was involved in all steps of proviral DNA synthesis. These observations have since been extensively borne out (3,9,13,37,60,61,91,101-103,180,214,215).

In the following sections we will briefly review the seminal role of NC in the fate of the HIV-1 full length RNA from mRNA encoding Gag and Gag-Pol to the genomic RNA in a dimeric form coated with hundreds of NC molecules present in the interior of the viral particle. Emphasis will be given to the implications of NC in the balance between genomic RNA translation and packaging, and on the mutual recognition between NC and the genomic RNA during virus assembly.

Understanding the fate of the genomic RNA, from translation to packaging.

In retroviruses and HIV-1 in particular, the full-length viral RNA acts both as a messenger and genomic RNA (29,38,61,73,127). The balance between these two key roles must be maintained to allow efficient virus replication. Since a genomic RNA molecule cannot ensure both functions concomitantly, this raised the question of how genomic RNA translation and packaging are coordinated (29,39,61,135). For the sake of simplicity, the genomic RNA, either messenger or pregenomic, has been named gRNA.

How can gRNA translation and packaging be linked? As for the host mRNAs, the viral gRNA is capped and polyadenylated (176) and its translation is dependent upon the host translational machinery and is regulated by its 5' untranslated region, the leader domain (34,42,202). The 5' leader of HIV-1 gRNA is composed of several genetic elements that largely orchestrate virus replication (15,17,107). The processes of gRNA translation and packaging are determined by the viral 5' Internal Ribosome Entry Segment (IRES) and its packaging signal (y), elements that share their primary sequences, but most probably differ in their secondary and tertiary structures (Figs. 1 and 2). Translation of the gRNA of some retrotransposons and retroviruses can proceed through a cap-independent mechanism, via an IRES (8,25,26,65,138,139161,210). The IRES directly recruits 40S ribosomal subunits in a 5' end independent fashion. The molecular mechanism by which the host translation apparatus recognizes the retroviral IRES is unknown, but for other viral IRESes canonical initiation factors as well as specific cellular proteins, IRES transacting factors (ITAFs), participate in the recognition process (4,15,118,124,168,169186). HIV-1 harbors two IRESes, one within the Gag open reading frame (ORF) (40K-IRES) (36), responsible for the synthesis of a 40-kDa Gag isoform and the other within the 5'leader, the HIV-1 IRES (34). This is not without precedent as multiple IRESes have been described for c-myc (157), vascular endothelial growth factor (117) and cricket paralysis virus (212) mRNAs.

Little is known on the molecular mechanism driving the HIV-1 IRES. However, the dual mechanism of translational initiation (5'cap and IRES-dependent) added to IRES redundancy suggests that control of translation of the HIV-1 gRNA plays an essential role in the regulation of virus replication. Indeed, the HIV-1 IRES overlaps with important functional elements (34) (Fig. 1, 2): the PBS, the dimer initiation site (DIS), the 5' SD and the major determinants of y (2,14, 17, 45,46,108,134,143). Similar to the IRESes of HCV (102), some members of the picornaviridae (33), ornithine decarboxylase (ODC) (173), c-Myc, and p58PITSLRE (50), the HIV-1 IRES is active during the G2/M phase of the cell cycle (34). Considering that 40S ribosome recruitment by IRESes appears to be dependent upon RNA secondary and tertiary structures, it is very likely that structural changes of the IRES are decisive in determining its activity. These structural modifications would act as a molecular switch that decides the fate of the HIV-l gRNA from translating ribosomes to Gag-NC directed packaging (19,120,121). Similar molecular models are proposed for poliovirus (90) and RSV (29,65,199). In agreement with this possibility, the 5'leader of HIV-1 gRNA can adopt two mutually exclusive secondary structures, defined as the branched multiple hairpin (BMH) and the long-distance interactions (LDI) structures (20,119,120,121). BMH promotes formation of the PBS, DIS, SD, and psi stem-loops, while the LDI engenders alternative base pairings that disrupt the DIS hairpin loop (120,121). The region of the HIV-1 leader, that includes the Gag start codon at positions 336-338, also folds differently depending on the LDI and BMH structures. Nucleotides 334-344 form part of an extended hairpin structure in the LDI conformation (108-110), whereas in the BMH structure they are engaged in novel base pairings with the upstream U5 region (nt 105 to 115). This U5-AUG duplex (1) in the BMH structure occludes the Gag start codon, most probably preventing Gag translation and favoring gRNA packaging (1). Consequently, the BMH and LDI conformations are expected to differ in their ability to confer gRNA dimer formation and to drive Gag synthesis (Fig. 1).


Figure 1. Gag-NC is a major determinant in the switch from messenger to genomic RNA. Upon synthesis, HIV-1 genomic RNA is initially recognized as the messenger RNA for Gag production. Newly made Gag molecules bind the gRNA via the NC domain causing conformational rearrangements of the 5' leader (1, 108,110,190). The structural modifications of the gRNA promoted by Gag-NC expose the cis-acting elements required for gRNA dimerization and packaging (DIS/y), occluding the RNA structures required for protein synthesis (right) (34). The overall effect of the RNA structural rearrangements in the 5' leader most probably results in the inhibition of translation (AUG in the small box), promoting gRNA dimerization and packaging. In this model the gRNA structures are adapted from (1).



Figure 2. The y signal of HIV-1 gRNA. The HIV-1 y is thought to be composed of four stem loops (SL). The high affinity binding sites are in gray. The Gag initiation codon is indicated. The major splice donor site (SD) is indicated by the arrow.


Based on current understanding of Gag-NC-RNA interactions, a reasonable model that links mRNA translation and gRNA packaging is the following: (i) During the early stages of viral replication, the HIV-1 gRNA is recognized by the cellular translation apparatus as a standard 5' capped and polyadenylated mRNA. At this stage both the 5'cap structure and the IRES element function, in an unknown fashion, to initiate synthesis of Gag and Gag-Pol polyproteins. (ii) Major changes in the cell cycle such as the viral induced G2/M growth arrest occur as viral proteins like VPR accumulate (95,123,136,144). (iii) In G2/M cap-dependent translation initiation is suppressed (174,175), but the HIV-1 IRES can ensure synthesis of Gag and Gag-Pol (34,190). (iv) It is conceivable that the level of Gag will play a major role in determining the fate of the translated gRNA (124). Newly formed Gag molecules will bind the gRNA via NC, probably causing conformational rearrangements of the 5' leader (1,120,121,126,206). Transconformation of gRNA structural elements by Gag-NC should result in the inhibition of translation as observed for RSV (29,167,199) and expose the structural elements required to chaperone gRNA dimerization and the packaging process (DIS/y) (1,59,120,121,184,195) (Fig. 1).

NC preference for single stranded domains of the psi signal and implications for gRNA packaging.

To understand how neo-synthesized Gag-NC molecules selectively discriminate the gRNA from the large excess of cellular and spliced viral RNAs within the infected cell, the binding parameters (stoichiometry and binding constants) of HIV-1 NCp7 to the psi signal were investigated. Since the length of psi (about 110 nt) precludes a reliable determination of the binding stoichiometry of NC to psi, this question has been addressed with its four individual stem-loops, SL1 to SL4. Most studies reveal a binding stoichiometry of one NC per SL (6,7,14,17,66,196,197,211), suggesting that each SL is characterized by a unique strong NC binding site. In agreement with structures revealed by NMR (6,7,66), mutational studies indicate that this NC site is located on the loop of the SL (66,142,166,196). Additional NC binding sites were observed only at high RNA concentrations (7) or in low salt conditions (142). However, the affinity of NC for these additional sites is at least 100 fold lower than that for the loop itself, confirming the preference of NC for single-stranded sequences (7,86,211). Studies with SL3 also revealed the formation of complexes composed of one NC and two SL3 RNAs, suggesting that NC may, to some extent, promote SL3 dimerization (191,196). The binding constants of NC to the different SL domains have been determined through different approaches. Originally, filter-binding assays and GST-NCp15 (46) returned binding constants of 2.5 x 106 M-1 for SL2 and 5 x 106 M-1 for the other SLs. Later, the affinity of mature NCp7 for the SLs was assessed by fluorescence spectroscopy (142,166,196,211), gel electrophoresis (7,66,196) and isothermal titration calorimetry (6). Even though experimental conditions somewhat varied, it can be concluded that NCp7 affinity for SL2 and SL3 is in the 107 M-1 range (6,7,142,196,211) and that for SL1 and SL4 it is approximately 3 and 10-fold less, respectively. By characterizing the binding of NC to different SL mutants, the GXG motif, which is common to the loops of all four SLs, was identified as a major determinant for NC binding (86,196,211).

How is the strong NC-loop interaction achieved?

All NC-oligonucleotide structures so far resolved show that a major contribution is provided by NC Trp37/Guanine stacking (6,66,150). NC-oligonucleotide complexes are further stabilized by 5 to 6 ionic interactions between the basic NC amino-acids and the SL phosphate groups. Strong binding of NC to the SL also requires some conformational flexibility of the GXG motif (7). In SL4, this flexibility is prevented by the formation of additional H-bonds between G5 and A3 of the GAGA tetraloop, resulting in reduced NC affinity (see above) (7).

NC binding sites and selection of the genomic RNA.

A consequence of the strong sequence (GXG) and structure (loop) requirements for NCp7-nucleic acid interaction is the large decrease of potential binding sites as compared with the canonical binding model where the nucleic acid is viewed as a lattice of overlapping sites with identical affinities (145). This supports the notion that no extreme binding constant is required to drive selective NC binding to a limited number of binding sites. Thus, selective recognition of the gRNA is probably achieved by Gag-NC molecules binding to SL1, SL2 and SL3 of the psi signal (Fig. 2). As SL1 is considered to be the DIS (179), binding of Gag-NC molecules to the three loop structures is thought to chaperone gRNA dimerization. This, in turn, should increase local gRNA and Gag concentrations and change the fate of the gRNA from messenger to pregenomic.

How do Gag-NC-SL1/DIS interactions promote gRNA dimerization?

NC-promoted chaperoning of HIV-1 gRNA dimerization was first established in vitro using the 5'leader RNA and NCp15 (NCp7-p6) under physiological conditions (59,69,71). Later, in HIV-1 subtype A or B, dimerization was found to rely on the inverted repeat sequence of the loop, GUGCAC or GCGCGC, respectively (154), and to proceed in a two step fashion. The first step, corresponds to an intermolecular loop-loop interaction between two SL1 motifs with six base pairs (the kissing complex, Fig. 3, left) (55,79,80). Next, the extended duplex, which involves extensive SL1/SL1 base pairing interactions, is formed between the two RNA molecules (80,94). In in vitro experiments carried out under physiological conditions, NC appears to promote formation of the extended stable duplex (Fig. 3 right) (82,154,185), mainly by chaperoning the most stable structure (53,110,111,209,214).

Figure 3. Proposed scheme of DIS sequence dimerization. Schematic representation of the NC-induced structural conversion of the DIS sequence from the kissing complex to the extended duplex. The palindromic sequence involved in the formation of the kissing complex is shown in gray.


Preferential packaging of two copies of the gRNA seems to be a general rule in the assembly of retroviruses (48,61,78,81,128,213). This phenomenon has important implications on viral variability (see last §) (48,114,115,205). It is therefore reasonable to ask if the Gag-NC directed gRNA dimerization is important in the course of HIV-1 assembly. Deleting or mutating the SL1/DIS sequence was found not only to reduce gRNA dimerization and packaging but also virus production was diminished and infectivity impaired (18,132,164,165). Interestingly, despite the reduction in gRNA dimerization, this process was far from totally abolished suggesting that Gag-NC chaperones formation of dimeric gRNA by several means. In fact, deletion of a strong NC binding site, the A-U large loop connecting SL2 to SL3 in psi (Fig. 2), not only caused a marked inhibition of in vitro NC-mediated dimerization, but also impaired gRNA packaging, viral nucleoid structure and virus replication in vivo (45,59). These observations further support the notion that gRNA dimerization can be achieved by a number of different routes and that the dimeric genome is a major player not only in Gag-NC assembly but also in virus structure and replication (44,45,155,156).

HIV-1 NCp7 structure and its relevance to genomic RNA recognition.

NMR-derived structures proposed for HIV-1 NCp7 and NC-RNA complexes have been instrumental in aiding our understanding at the molecular level of the process of gRNA selection by Gag-NC. All abundant retroviruses possess an NC characterized by one or two highly conserved zinc fingers (ZF) of the form CysX2CysX4HisX4Cys (51,61). In HIV-1, NCp7 has two ZFs each containing an aromatic residue, linked by the basic sequence RAPRKKG (Fig. 4). NMR and fluorescence studies of free NC in solution have shown that the affinity of Zn2+ for the fingers is very high (Ka ~1014 M-1) (32,146). NMR-derived structures of each ZF showed that the peptide sequence is stably folded around the ion (31,138,201) and that this structural arrangement is nearly identical for both ZFs (151,201). Similar features apply to the ZF of MoMuLV NCp10 (67). In addition, the two ZFs and the RAPRKKG linker can adopt a globular conformation leading to spatial proximity, modulated by the relative flexibility of the linker, between Phe16 and Trp37 (151). In contrast to the ZFs, the N- and C-terminal regions of NCp7 do not show any defined structure (151).

Early studies reported that substitution of a Ser or Ala for Cys in position 23 caused a loss of the high affinity for the zinc ion, resulting in ZF unfolding. Mutant viruses produced by DNA transfection of cells were replication defective (68,99,162). Mutations in which Cys23 was substituted by His did not modify the affinity for the zinc ion but affected ZF folding, abrogating the spatial proximity of the fingers (61,68,72,98,99) (Fig. 4) as well as virus infectivity (61,99). A number of other ZF mutations aimed at disrupting folding of the fingers (177,178) also lead to modifications of virion nucleoid structure with a concomitant loss of virus infectivity (2,61,72,99,162). These findings support the notion that a bona fide three dimensional structure of the NC central globular region plays a key role in virus replication (61,68,99,162).

Figure 4. 3-D structure of NCp7 and mutant H23C. The central domain of NCp7 wild type (wt) is shown on the left. The N-terminal zinc finger (ZF1) is at the bottom while the C-terminal zinc finger (ZF2) is at the top. The Zn2+ ion is represented by a small green marble. The RAPRKKG linker is in purple. Note the proximity of Phe16 (ZF1) and Trp37 (ZF2) in the structure (aromatic rings in red). Mutation H23C, shown on the right, causes a disruption of the central globular structure as evidenced by the opposing arrangement of Phe16 and Trp37. Note that this mutation results in the production of non infectious viral particles with structural abnormalities within the viral core.


As described above, NC has strong nucleic acid binding and chaperoning properties (53,70,110). Genomic RNA (gRNA) recognition is probably initiated by interactions between the ZFs of Gag-NC and the psi determinants thought to be the unpaired sequences within the SL determinants of the psi signal. This raises questions concerning the molecular mechanisms governing NC binding to the psi element. As discussed, it is likely that more than one NC molecule at a time recognizes psi, rendering the recognition process very selective. However, the structural analysis of such a high molecular mass NC-RNA complex is considered to be extremely difficult. Currently, only the 3-D structure for one molecule of NC bound to SL3 or part of SL2 in a DNA form is available (Fig. 5) (66,150). In these complexes, the backbone of each ZF is preserved and the spatial proximity between the Phe16 of the first ZF and Trp37 of the second ZF is stabilized (66,150). Interestingly, the rather large flexibility of the RAPRKKG linker appears to be the way by which NC can interact with either single or double stranded nucleic acids. In the NC(1-55)/SL3 complex, the ZF preferentially interacts with the single stranded loop as in the NC/d(ACGCC) complex. In the NC(1-55)/SL3 structure the basic N-terminal region of NC, non-structured in the free form, adopts an helical conformation fitting the double-stranded stem. Comparison of the two 3D conformations emphasizes the critical role of Trp37 in the second ZF since it was found stacked to a guanine residue in both complexes (Fig. 5) (66,150). Therefore Trp37 appears to be a key NC determinant for nucleic acid recognition in general, and of the gRNA in particular (74,181). The role of the RAPRKKG linker (150,162,177) and basic N-terminus (27) can be envisaged as reinforcing and modulating nucleic acid recognition and subsequent chaperoning (70,110,130,207). Thus Trp37 would select the theme and the basic regions would perform 'art variations'.

Figure 5. 3-D structure of NCp7-SL3 RNA and NCp7-dACGCC complexes. The structures of NCp7-SL3 RNA and NCp7-dACGCC complexes are shown on the left and right, respectively. The nucleic acids are shown in bright green and oriented bottom (5') to top (3'). NCp7 is oriented from left (N) to right (C). Note the stacking of Trp37 to the guanine residue in both structures. In addition, the N-terminal domain of NCp7 and the RAPRKKG linker both interact with the nucleic acid molecule (dark blue).


Virus assembly; the current view.

Abundant published data on the fate of the genomic RNA and NC in respect of virus formation have tried to answer key questions on how and where viral assembly takes place. On this basis it is possible to postulate the following picture of gRNA and Gag-NC interactions: (i) the full length viral RNA is translated by a combination of Cap and IRES driven mechanisms to generate Gag and Gag-Pol. Accumulation of VPR arrests infected cells in G2/M (10,100,123,144,152,179) favoring gRNA synthesis and IRES mediated translation initiation. (ii) Newly made Gag molecules interact with the gRNA via NC (21-24,54,62,141), inhibiting translation and targeting the gRNA to the cell membrane (34,84,85). At this early stage, the selection of the gRNA is probably mediated by Gag-NC molecules through recognition of the psi signal by the NC zinc fingers, stabilized by ionic interactions between NC basic residues and the psi sequence. The multiple SL determinants of HIV-1 psi (21-23,54,134,170,184) that are positioned between the 5' SD and AUG of Gag ensure NC-mediated selection of the gRNA only (2,14,17,45,46,47,61,143,217). The mutual gRNA/Gag recognition can be viewed as a zip-like process since it probably requires one NC per SL and thus several NC per psi signal and, in addition, several NC-RNA interactions for each psi SL. (iii) Finally, accumulation of Gag-NC molecules on the gRNA will chaperone the conformational rearrangements of the 5' leader, gRNA dimerization and capture into the growing viral globule (22,23,46,76,126,127,130,133,141,217).


It seems that two platforms orchestrate virus assembly: firstly, the membrane, or outer platform, in which HIV-1 Gag molecules are anchored via the N-terminal part of the matrix domain (44,84,85,219). Secondly, the gRNA or interior platform acting as a scaffold molecule, nucleating Gag oligomerization and assembly (45,76,156,203). Finally, the Gag-Pol precursor is recruited into the viral globule (93,163) during assembly resulting in protease activation most probably due to the high local concentration of Gag-Pol. The protease-directed processing of Gag results in the genome being entirely coated with mature NC molecules that will later chaperone the annealing of primer tRNALys,3 to the PBS and the initiation of cDNA synthesis by reverse transcriptase (9,13,40,41,56,60,69,74,106,133,140,208,201,218). Lastly, NC will chaperone nucleoid condensation and stability (81,87,160,200). At the early stages of infection, NC will chaperone all the steps of the RT-mediated replication of the gRNA, from primer tRNA annealing to the PBS to the synthesis of the complete double stranded proviral DNA as well as viral genetic re-assortments by recombination in the course of cDNA synthesis (5,9,49,96,112,114,115,125,131,158,183,187,188). Also, a significant body of evidence favors the idea that NC can guide the integration process by preserving the LTR ir sequences and activating the integrase enzyme (37,91,129).

Conclusion and future prospects

In conclusion, NC either as Gag-NC or as the mature protein appears to be the 'high fidelity' partner of the genomic RNA, chaperoning functional rearrangements of the RNA structure, stability and bona fide conversion to proviral DNA by RT (53,61,99,131,180).

Addressing the following key areas in the years ahead should significantly advance our understanding of the molecular mechanisms underlying HIV-1 assembly: (i) a comprehensive view of gRNA selection by Gag-NC will require deciphering of the 3D structure of HIV-1 psi in the monomeric and dimeric forms, alone or associated with NC molecules. The affinity of the immature and mature forms of NC (Gag-NC, NCp15, NCp7(1-71), NCp7(1-55) (71,109) for SL, psi and psi mutants will need to be compared. Since SIV gRNA can participate in HIV-1 Gag assembly (although not reciprocally) it will be of interest to compare the affinity of HIV-1 Gag and SIV Gag for SL and psi, in both homologous and heterologous combinations. (ii) Little is known on the extent of translational regulation in HIV-1 and in retroviruses generally. It would seem beneficial therefore to further investigate the binding of cellular translation initiation factors (e.g. eIF4G) to HIV-1, SIV and other retroviral IRESes and to determine in greater detail their modulatory effects on viral translation during the different phases of the cell cycle. (iii) The 5' HIV leader contains multiple genetic determinants essential in all stages of virus replication. Secondary structures within the leader have been proposed, however the possibility of long distance interactions between the leader and the 3' UTR requires greater attention as these are potentially of key importance in gRNA structure and replication, as suggested by evidence from RSV and retrotransposons of yeast (52,58,88). Such 5'-3' gRNA interactions could greatly facilitate translation, assembly and reverse transcription. (iv) Little is known about the dynamics of the viral particle between completion of assembly and budding out of the cell. Evidence that reverse transcription begins in newly made particles (56,141,208,216,218) favors the notion these are fully functional as soon as their interior is formed. However, little is known about the cellular route(s) particles follow to leave the cell.

Finally, in view of the fundamental role of NC during the HIV life-cycle, a concerted effort aimed at the development of drugs to abrogate its functions would seem amply justified (28,75,182).


We wish to thank Nelly Morellet and Michaël Rau (UK) for suggestions and corrections. Thanks are due to the ANRS, the ENS de Lyon, the INSERM, the European Community, Sidaction and the ARC for their continuous support. MLL was supported by a CIHR postdoctoral fellowship.

Abbreviations. HIV, human immunodeficiency virus. IRES, internal ribosome entry signal. MuLV, murine leukemia virus. NC, nucleocapsid protein. RT, reverse transcriptase. ZF, zinc finger. RSV, Rous sarcoma virus. SIV, simian immunodeficiency virus.


[1] Abbink, T. E. & Berkhout, B. (2003). A novel long distance base pairing interaction in human immunodeficiency virus type 1 RNA occludes the Gag start codon. J. Biol Chem. 28;278:11601-11.

[2] Aldovini, A. & Young, R. A. (1990). Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J. Virol. 64:1920-6.

[3] Allain, B., M. Lapadat-Tapolsky, C. Berlioz and J-L. Darlix. (1994). Trans-activation of the minus-strand DNA transfer by nucleocapsid protein during reverse transcription of the retroviral genome. EMBO J. 13:973-981.

[4] Ali, N., Pruijn, G. J., Kenan, D. J., Keene, J. D. & Siddiqui, A. (2000). Human La antigen is required for the hepatitis C virus internal ribosome entry site-mediated translation. J. Biol. Chem. 275:27531-40.

[5] Alizon, M., Wain-Hobson, S., Montagnier, L. & Sonigo, P. (1986). Genetic variability of the AIDS virus : nucleotide sequence analysis of two isolates from African patients. Cell 46:63-74.

[6] Amarasinghe, G. K., De Guzman, R. N., Turner, R. B., Chancellor, K. J., Wu, Z. R. & Summers, M. F. (2000). NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi-RNA packaging signal. Implications for genome recognition. J. Mol. Biol. 301:491-511.

[7] Amarasinghe, G. K., Zhou, J., Miskimon, M., Chancellor, K. J., McDonald, J. A., Matthews, A. G., Miller, R. R., Rouse, M. D. & Summers, M. F. (2001). Stem-loop SL4 of the HIV-1 psi RNA packaging signal exhibits weak affinity for the nucleocapsid protein. structural studies and implications for genome recognition. J. Mol. Biol. 314:961-70.

[8] Attal, J., Theron, M. C., Taboit, F., Cajero-Juarez, M., Kann, G., Bolifraud, P. & Houdebine, L. M. (1996). The RU5 ('R') region from human leukaemia viruses (HTLV-1) contains an internal ribosome entry site (IRES)-like sequence. FEBS Lett 392:220-4.

[9] Auxilien S, Keith G, Le Grice SF, Darlix JL. (1999). Role of post-transcriptional modifications of primer tRNALys,3 in the fidelity and efficacy of plus strand DNA transfer during HIV-1 reverse transcription. J. Biol. Chem. 274(7):4412-4420.

[10] Ayyavoo, V., Mahalingam, S., Rafaeli, Y., Kudchodkar, S., Chang, D., Nagashunmugam, T., Williams, W. V. & Weiner, D. B. (1997). HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro. J Leukoc Biol 62:93-9.

[11] Baltimore D. (1970) RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209-1211.

[12] Baltimore, D. (1985). Retroviruses and retrotransposons : the role of reverse transcription in shaping the eukaryotic genome. Cell 40:481-482.

[13] Barat, C., Lullien, V. Schatz, O. Grüninger-Leitch, M., Le Grice, S., Nugeyre, M.-T., Barré-Sinoussi, F. and Darlix, J.-L. (1989). HIV-1 reverse transcriptase specifically interacts with the anti-codon domain of its cognate primer tRNA. EMBO J. 8:3279-3285.

[14] Baudin, F., Marquet, R., Isel, C. Darlix, J.-L., Ehresmann, B. and Ehresmann, C. (1993). Functional sites in the 5' region of HIV1 RNA form defined structural domains. J. Mol. Biol. 229:382-397.

[15] Belsham, G. J. & Sonenberg, N. (2000). Picornavirus RNA translation: roles for cellular proteins. Trends Microbiol 8:330-5.

[16] Benedetti, E. & Bernhard, W. (1958). Recherches untrastructurales sur le virus de la leucémie érythroblastique du poulet. J. Ult. Res. 1:309-336.

[17] Berkhout, B. (1996). Structure and function of the human immunodeficiency virus leader RNA. Prog Nucleic Acid Res Mol Biol 54:1-34.

[18] Berkhout B, van Wamel JL. (1996). Role of the DIS hairpin in replication of human immunodeficiency virus type 1. J. Virol. 70:6723-32.

[19] Berkhout, B. & van Wamel, J. L. (2000). The leader of the HIV-1 RNA genome forms a compactly folded tertiary structure. RNA 6:282-95.

[20] Berkhout, B., Ooms, M., Beerens, N., Huthoff, H., Southern, E. & Verhoef, K. (2002). In vitro evidence that the untranslated leader of the HIV-1 genome is an RNA checkpoint that regulates multiple functions through conformational changes. J. Biol. Chem. 277:19967-75.

[21] Berkowitz, R. D., Luban, J. & Goff, S. P. (1993). Specific binding of human immunodeficiency virus type 1 gag polyprotein and nucleocapsid protein to viral RNAs detected by RNA mobility shift assays. J. Virol. 67:7190-200.

[22] Berkowitz, R. D. & Goff, S. P. (1994). Analysis of binding elements in the human immunodeficiency virus type 1 genomic RNA and nucleocapsid protein. Virology 202:233-46.

[23] Berkowitz, R. D., Ohagen, A., Hoglund, S. & Goff, S. P. (1995). Retroviral nucleocapsid domains mediate the specific recognition of genomic viral RNAs by chimeric Gag polyproteins during RNA packaging in vivo. J. Virol. 69:6445-56.

[24] Berkowitz, R. D., Hammarskjold, M. L., Helga-Maria, C., Rekosh, D. & Goff, S. P. (1995). 5' regions of HIV-1 RNAs are not sufficient for encapsidation: implications for the HIV-1 packaging signal. Virology 212:718-23.

[25] Berlioz, C., Torrent, C. & Darlix, J. L. (1995). An internal ribosomal entry signal in the rat VL30 region of the Harvey murine sarcoma virus leader and its use in dicistronic retroviral vectors. J. Virol. 69:6400-7.

[26] Berlioz, C. & Darlix, J. L. (1995). An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors. J. Virol. 69:2214-22.

[27] Berthoux, L., Péchoux, C., Ottmann, M., Morel, G. and Darlix, J.-L. (1997) Mutations in the N-terminal domain of HIV-1 nucleocapsid protein affect virion core structure and proviral DNA synthesis. J. Virol. 71:6937-6981.

[28] Berthoux, L., Christine Péchoux and Jean-Luc Darlix. 1999. Multiple Effects of an Anti-HIV Nucleocapsid Inhibitor on Virus Morphology and Replication. J. Virol. 73:10000-10009.

[29] Bieth, E., Gabus, C. & Darlix, J. L. (1990). A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro. Nucleic Acids Res 18:119-27.

[30] Bishop, J. M. (1983). Cellular oncogenes and retroviruses. Annu. Rev. Biochem. 52:301-354.

[31] Bombarda, E., Cherradi, H., Morellet, N., Roques, B. P. & Mely, Y. (2002). Zn(2+) binding properties of single-point mutants of the C-terminal zinc finger of the HIV-1 nucleocapsid protein: evidence of a critical role of cysteine 49 in Zn(2+) dissociation. Biochemistry 41:4312-20.

[32] Bombarda, E., Morellet, N., Cherradi, H., Spiess, B., Bouaziz, S., Grell, E., Roques, B. P. & Mely, Y. (2001). Determination of the pK(a) of the four Zn2+-coordinating residues of the distal finger motif of the HIV-1 nucleocapsid protein: consequences on the binding of Zn2+. J. Mol. Biol. 310:659-72.

[33] Bonneau, A. M. & Sonenberg, N. (1987). Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis. J. Biol. Chem. 262:11134-9.

[34] Brasey, A., López-Lastra, M., Ohlmann, T., Beerens, N., Berkhout, B., Darlix, J.-L. & Sonenberg, N. (2003). The leader of HIV-1 genomic RNA harbors an Internal Ribosome Entry Segment (IRES) that is active during the G2/M phase of the cell cycle. J. Virol. 77:3939-3949.

[35] Brugge, J. & Erickson, R. (1977). Identification of a transformation specific antigen induced by an avian sarcoma virus. Nature 269:346-348.

[36] Buck, C. B., Shen, X., Egan, M. A., Pierson, T. C., Walker, C. M. & Siliciano, R. F. (2001). The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site. J. Virol. 75:181-91.

[37] Buckman JS, Bosche WJ, Gorelick RJ. (2003). Human immunodeficiency virus type 1 nucleocapsid zn(2+) fingers are required for efficient reverse transcription, initial integration processes, and protection of newly synthesized viral DNA. J Virol. 77:1469-1480.

[38] Butsch, M. & Boris-Lawrie, K. (2000). Translation is not required to generate virion precursor RNA in human immunodeficiency virus type 1-infected T cells. J. Virol. 74:11531-7.

[39] Butsch, M. & Boris-Lawrie, K. (2002). Destiny of unspliced retroviral RNA: ribosome and/or virion? J. Virol. 76:3089-94.

[40] Cen S, Huang Y, Khorchid A, Darlix JL, Wainberg MA, Kleiman L. (1999). The role of Pr55(gag) in the annealing of tRNA3Lys to human immunodeficiency virus type 1 genomic RNA. J. Virol. 73(5):4485-4488.

[41] Chan B, Weidemaier K, Yip WT, Barbara PF, Musier-Forsyth K. (1999). Intra-tRNA distance measurements for nucleocapsid protein dependent tRNA unwinding during priming of HIV reverse transcription. Proc. Natl. Acad. Sci. USA 96(2):459-464.

[42] Chang, Y. N., Kenan, D. J., Keene, J. D., Gatignol, A. & Jeang, K. T. (1994). Direct interactions between autoantigen La and human immunodeficiency virus leader RNA. J. Virol. 68:7008-20.

[43] Chen, M., Garon, C. and Papas, T. (1980). Native ribonucleoprotein is an efficient transcriptional complex of avian myeloblastosis virus. Proc. Natl. Acad. Sci. USA 77:1296-1300.

[44] Cimarelli A, Darlix JL. (2002). Assembling the human immunodeficiency virus type 1. Cell Mol Life Sci. 59(7):1166-1184.

[45] Clavel, F. & Orenstein, J. (1990). A mutant of HIV-1 with reduced RNA packaging and abnormal particle morphology. J. Virol. 64:5230-5234.

[46] Clever, J., Sassetti, C. & Parslow, T. G. (1995). RNA secondary structure and binding sites for gag gene products in the 5' packaging signal of human immunodeficiency virus type 1. J. Virol. 69:2101-9.

[47] Clever, J. L., Mirandar, D., Jr. & Parslow, T. G. (2002). RNA structure and packaging signals in the 5' leader region of the human immunodeficiency virus type 1 genome. J. Virol. 76:12381-7.

[48] Coffin, J. (1979). Structure, replication and recombination of retrovirus genomes : some unifying hypothesis. J. Gen. Virol. 42:1-17.

[49] Coffin, J. (1995). HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483-489.

[50] Cornelis, S., Bruynooghe, Y., Denecker, G., Van Huffel, S., Tinton, S. & Beyaert, R. (2000). Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol Cell 5:597-605.

[51] Covey, S. N. (1986). Amino acid sequence homology in GAG region of reverse transcribing elements and the coat protein gene of cauliflower mosaic virus. Nucleic Acids Res. 14:623-633.

[52] Cristofari G, Bampi C, Wilhelm M, Wilhelm FX, Darlix JL. (2002). A 5'-3' long-range interaction in Ty1 RNA controls its reverse transcription and retrotransposition. EMBO J. 21(16):4368-79.

[53] Cristofari G, Darlix JL. (2002). The ubiquitous nature of RNA chaperone proteins. Prog Nucleic Acid Res Mol Biol. 72:223-268.

[54] Dannull, J., Surovoy, A., Jung, G. and Moelling, K. (1994). Specific binding of HIV-1 nucleocapsid protein to PSI RNA in vitro requires N-terminal zinc finger and flanking basic amino acid residues. EMBO J. 13:1525-1533.

[55] Dardel, F., Marquet, R., Ehresmann, C., Ehresmann, B. & Blanquet, S. (1998). Solution studies of the dimerization initiation site of HIV-1 genomic RNA. Nucleic Acids Res 26:3567-71.

[56] Darlix JL, Bromley PA, Spahr PF (1977). New procedure for the direct analysis of in vitro reverse transcription of Rous sarcoma virus RNA. J. Virol. 22(1):118-129.

[57] Darlix, J.-L. and Spahr, P-F.(1982). Binding sites of viral protein p19 onto RSV RNA and possible control of viral functions. J. Mol. Biol. 160:147-161.

[58] Darlix, J.-L. (1986). Control of RSV genome translation and packaging by the 5' and 3' untranslated sequences. J. Mol. Biol. 189:421-434.

[59] Darlix, J-L, Gabus, C., Nugeyre, M.-T., Clavel, F. and Barré-Sinoussi, F. (1990). Cis elements and trans acting factors involved in the RNA dimerization of HIV-1. J. Mol. Biol. 216:689-699.

[60] Darlix, J.-L., Vincent, A., Gabus, C., de Rocquigny, H. and Roques, B. (1993). Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV1 RNA. Comptes Rendus Acad. Sci., 316:763-771.

[61] Darlix, J.-L., Lapadat-Tapolsky, M., de Rocquigny, H. and Roques, B. (1995). First glimpses at structure-function relationships of the nucleocapsid protein of retroviruses. Review article. J. Mol. Biol. 254:523-537.

[62] Damgaard, C. K., Dyhr-Mikkelsen, H. & Kjems, J. (1998). Mapping the RNA binding sites for human immunodeficiency virus type-1 gag and NC proteins within the complete HIV-1 and -2 untranslated leader regions. Nucleic Acids Res 26:3667-76.

[63] Davis, N. and Rueckert. 1972. Properties of a ribonucleoprotein particle isolated from NP 40 treated RSV. J. Virol. 10:1010-1020.

[64] Davis J, Scherer M, Tsai WP, Long C. (1976). Low-molecular- weight Rauscher leukemia virus protein with preferential binding for single-stranded RNA and DNA. J. Virol. 18:709-718.

[65] Deffaud, C. & Darlix, J. L. (2000). Rous sarcoma virus translation revisited: characterization of an internal ribosome entry segment in the 5' leader of the genomic RNA. J. Virol. 74:11581-8.

[66] De Guzman, R. N., Wu, Z. R., Stalling, C. C., Pappalardo, L., Borer, P. N. and Summers M. F. Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element. Science 1998, 279:384-38.

[67] Déméné, H., Jullian, N., Morellet, N., de Rocquigny, H., Cornille, F., Maigret, B., Roques, B. P. (1994) Three-dimensional 1H NMR structure of the nucleocapsid protein NCp10 of Moloney murine leukemia virus. J Biomol NMR 4,153-70.

[68] Deméné, H., Dong, C., Ottmann, M., Rouyez, M., Jullian, N., Morellet, N., Mely, Y., Darlix, J.-L., Fournié-Zaluski, M.-C., Saragosti, S. and Roques, B. (1994b). 1H NMR structure and biological studies of the His23 >Cys mutant nucleocapsid protein of HIV-1 indicate that the conformation of the first zinc finger is critical for virus infectivity. Biochemistry 33:11707-11716.

[69] De Rocquigny, H., Gabus, C., Vincent, A., Fournié-Zaluski, M.-C., Roques, B. and Darlix, J.-L. (1992). Viral RNA annealing activities of HIV-1 nucleocapsid protein require only peptide domains outside the zinc fingers. Proc. Natl. Acad. Sci. USA, 89:6472-6476.

[70] Dib-Hajj, F., Khan, R. and Giedroc, D. P. (1993). Retroviral nucleocapsid proteins possess potent nucleic acid strand renaturation activity. Protein Science, 2:231-243.

[71] Di Marzo-Veronese, F., Rahman, R., Copeland, T., Orsozlan, S., Gallo, R. C. and Sarnagadharan, M. G. (1987). Immunological and chemical analysis of P6, the carboxyl terminal fragment of HIV P15. AIDS Res. & Human Retroviruses, 3:253-264.

[72] Dorfman, T., Luban,J., Goff, S., Haseltine, W. and G. Göttlinger, H. (1993). Mapping of Functionally Important Residues of a Cysteine-Histidine Box in the Human Immunodeficiency Virus Type-1 Nucleocapsid Protein. J. Virol. 67:6159-6169.

[73] Dorman, N. & Lever, A. (2000). Comparison of viral genomic RNA sorting mechanisms in human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine leukemia virus. J Virol 74, 11413-

[74] Druillennec, S., Caneparo, A., de Rocquigny, H., Roques, B. P. Evidence of interactions between the nucleocapsid protein NCp7 and the reverse transcriptase of HIV-1. J Biol Chem 1999, 274, 11283-8.

[75] Druillennec, S., Dong, C. Z., Escaich, S.,Gresh, N., Bousseau, A., Roques, B. P. & Fournié-Zaluski, M. C. (1999). A mimic of HIV-1 NC protein impairs reverse transcription and display antiviral activity. Proc. Natl. Acad. Sci., 96(9), 4886-4891.

[76] Echols, H. (1990). Nucleoprotein structures initiating DNA replication, transcription and site-specific recombination. J. Biol. Chem. 265:14697-14700.

[77] Ellermann, V. & Bang, O. (1908). Experimentelle Leukämie bei hühnern. Zentralbl. Backteriol. 46:595-609.

[78] Embretson, J. and Temin, H. (1987). Lack of competition results in efficient packaging of heterologous murine retroviral RNAs in reticuloendotheliosis virus encapsidation-minus RNAs by the reticuloendotheliosis virus helper cell line. J. Virol. 61:2675-2683.

[79] Ennifar, E., Walter, P., Ehresmann, B., Ehresmann, C. & Dumas, P. (2001). Crystal structures of coaxially stacked kissing complexes of the HIV-1 RNA dimerization initiation site. Nat Struct Biol 8:1064-1068.

[80] Ennifar, E., Yusupov, M., Walter, P., Marquet, R., Ehresmann, B., Ehresmann, C. & Dumas, P. (1999). The crystal structure of the dimerization initiation site of genomic HIV-1 RNA reveals an extended duplex with two adenine bulges. Structure Fold Des. 7(11):1439-1449.

[81] Feng YX, Copeland TD, Henderson LE, Gorelick RJ, Bosche WJ, Levin JG, Rein A. (1996). HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in vitro. Proc Natl Acad Sci U S A. 93:7577-7581.

[82] Feng YX, Campbell S, Harvin D, Ehresmann B, Ehresmann C, Rein A. (1999). The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid chaperone activity: possible role in dimerization of genomic RNA and placement of tRNA on the primer binding site. J Virol. 73:4251-4256.

[83] Fleissner E, Tress E. (1973). Isolation of a ribonucleoprotein structure from oncornaviruses. J Virol. 12:1612-1615.

[84] Freed, E., Orenstein, J., Buckler-White, A. and Martin, M. (1994). Single amino acid changes in HIV-1 matrix protein block virus particle production. J. Virol. 68:5311-5320.

[85] Freed EO. (2002). Viral late domains. J. Virol. 76(10):4679-4687.

[86] Fisher RJ, Rein A, Fivash M, Urbaneja MA, Casas-Finet JR, Medaglia M, Henderson LE. (1998). Sequence-specific binding of human immunodeficiency virus type 1 nucleocapsid protein to short oligonucleotides. J. Virol. 72(3):1902-1909.

[87] Fu, W. and Rein, A. (1993). Maturation of dimeric viral RNA of MoMuLV. J. Virol. 67:5443-5449.

[88] Gabus, C., D. Ficheux, M. Rau, G. Keith, S. Sandmeyer and J-L. Darlix. (1998). The yeast Ty3 Retrotransposon contains a bipartite primer binding site and encodes nucleocapsid protein NCp9 functionally homologous to HIV-1 NCp7. EMBO J. 17:4873-4880.

[90] Gamarnik, A. V. & Andino, R. (1998). Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev 12:2293-304.

[91] Gao K, Gorelick RJ, Johnson DG, Bushman F. (2003). Cofactors for human immunodeficiency virus type 1 cDNA integration in vitro. J. Virol. 77:1598-1603.

[92] Garfinkel, D., Boeke, J. & Fink, G. (1985). Ty element transposition : reverse transcriptase and virus like particles. Cell 42:507-517.

[93] Gelderblom, H., Hausmann, E., Ozel, M., Pauli, G. & Koch, M. (1987). Fine structure of Human Immunodeficiency Virus (HIV) and immunolocalization of structural proteins. Virology 156:171-176.

[94] Girard, F., Barbault, F., Gouyette, C., Huynh-Dinh, T., Paoletti, J. & Lancelot, G. (1999). Dimer initiation sequence of HIV-1Lai genomic RNA: NMR solution structure of the extended duplex. J Biomol Struct Dyn 16:1145-57.

[95] Goh, W. C., Rogel, M. E., Kinsey, C. M., Michael, S. F., Fultz, P. N., Nowak, M. A., Hahn, B. H. & Emerman, M. (1998). HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 4:65-71.

[96] Goodrich, D. W., Duesberg, P. H. (1990). Retroviral recombination during reverse transcription. Proc. Natl. Acad. Sci. USA, 87:2052-2056.

[97] Gorelick RJ, Henderson LE, Hanser JP, Rein A. (1988). Point mutants of Moloney murine leukemia virus that fail to package viral RNA: evidence for specific RNA recognition by a "zinc finger-like" protein sequence. Proc. Natl. Acad. Sci. USA 85:8420-8424.

[98] Gorelick RJ, Nigida SM Jr, Bess JW Jr, Arthur LO, Henderson LE, Rein A. (1990). Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. J Virol. 64:3207-3211.

[99] Gorelick, R. J., Henderson, L. E., Hanser, J. P., and Rein, A. (1991). Roles of nucleocapsid cysteine arrays in retroviral assembly and replication: possible mechanisms in RNA replication. Advances in molecular biology and targeted treatment for AIDS. A. Kumar ed., Plenum press (NY, USA).

[100] Gummuluru, S. & Emerman, M. (1999). Cell cycle- and Vpr-mediated regulation of human immunodeficiency virus type 1 expression in primary and transformed T-cell lines. J. Virol. 73:5422-3540.

[101] Guo J, Henderson LE, Bess J, Kane B, Levin JG. (1997). Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self-priming from minus-strand strong-stop DNA. J. Virol. 71:5178-5188.

[102] Guo J, Wu T, Anderson J, Kane BF, Johnson DG, Gorelick RJ, Henderson LE, Levin JG.(2000). Zinc finger structures in the human immunodeficiency virus type 1 nucleocapsid protein facilitate efficient minus- and plus-strand transfer. J. Virol. 74(19):8980-8988.

[103] Guo J, Wu T, Kane BF, Johnson DG, Henderson LE, Gorelick RJ, Levin JG. (2002) Subtle alterations of the native zinc finger structures have dramatic effects on the nucleic acid chaperone activity of human immunodeficiency virus type 1 nucleocapsid protein. J Virol. 76(9):4370-4378.

[104] Hanafusa, H. (1969). Rapid transformation of cells by Rous sarcoma virus. Proc Natl Acad Sci USA. 63:318-325.

[105] Hansen, L., Chalker, D., and Sandmeyer, S. (1988). Ty3, a yeast retrotransposon associated with tRNA genes, has homology to animal retroviruses. Mol. Cell. Biol. 8:5245-5256.

[106] Hargittai MR, Mangla AT, Gorelick RJ, Musier-Forsyth K. (2001). HIV-1 nucleocapsid protein zinc finger structures induce tRNA(Lys,3) structural changes but are not critical for primer/template annealing. J. Mol. Biol. 312(5):985-997.

[107] Harrison, G. and Lever, A. (1992). The HIV-1 packaging signal and major splice donor site region have a conserved stable secondary structure. J. Virol. 66:4144-4153.

[108] Hayashi, T., Shioda, T., Iwakura, Y. & Shibuta, H. (1992). RNA packaging signal of human immunodeficiency virus type 1. Virology 188:590-9.

[109] Henderson, L., Bowers, M., Sowder, R., et al. (1992). Gag proteins of the highly replicative MN strain of HIV-1: posttranslational modifications, proteolytic processings and complete amino acid sequences. J. Virol. 66:1856-1865.

[110] Herschlag, D. (1995). RNA chaperones and the RNA folding problem. J. Biol. Chem. 270:20871-4.

[111] Herschlag, D., Khosla, M., Tsuchihashi, Z. & Karpel, R. L. (1994). An RNA chaperone activity of non-specific RNA binding proteins in hammerhead ribozyme catalysis. Embo J 13:2913-24.

[112] Ho, D., Neumann, A., Perelson, A., Chen, W., Leonard, J. and Markowitz, M. (1995). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-126.

[113] Honda, M., Kaneko, S., Matsushita, E., Kobayashi, K., Abell, G. A. & Lemon, S. M. (2000). Cell cycle regulation of hepatitis C virus internal ribosomal entry site-directed translation. Gastroenterology 118:152-62.

[114] Hu, W.-S. and Temin, H. (1990). Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc. Natl. Acad. Sci. USA, 87:1556-1560.

[115] Hu, W.-S. and Temin, H. M. (1990). Retroviral recombination and reverse transcription. Science, 250:1227-1233.

[116] Huebner, R. & Todaro, G. (1969). Oncogenes of RNA tumor viruses as determinants of cancer. Proc. Nat. Acad. Sci. USA 64, 1087-1094. Huthoff, H. & Berkhout, B. (2001). Mutations in the TAR hairpin affect the equilibrium between alternative conformations of the HIV-1 leader RNA. Nucleic Acids Res 29:2594-600.

[117] Huez, I., Creancier, L., Audigier, S., Gensac, M. C., Prats, A. C. & Prats, H. (1998). Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA. Mol Cell Biol 18:6178-90.

[118] Hunt, S. L. & Jackson, R. J. (1999). Polypyrimidine-tract binding protein (PTB) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 RNA. Rna 5:344-59.

[119] Huthoff, H. & Berkhout, B. (2002). Multiple secondary structure rearrangements during HIV-1 RNA dimerization. Biochemistry 41:10439-45.

[120] Huthoff, H. & Berkhout, B. (2001). Two alternating structures of the HIV-1 leader RNA. Rna 7:143-57.

[121] Huthoff, H. & Berkhout, B. (2001). Mutations in the TAR hairpin affect the equilibrium between alternative conformations of the HIV-1 leader RNA. Nucleic Acids Res 29:2594-600.

[122] Izumi, R. E., Valdez, B., Banerjee, R., Srivastava, M. & Dasgupta, A. (2001). Nucleolin stimulates viral internal ribosome entry site-mediated translation. Virus Res 76:17-29.

[123] Jowett, J. B., Planelles, V., Poon, B., Shah, N. P., Chen, M. L. & Chen, I. S. (1995). The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J. Virol. 69:6304-13.

[124] Kaminski, A. & Jackson, R. J. (1998). The polypyrimidine tract binding protein (PTB) requirement for internal initiation of translation of cardiovirus RNAs is conditional rather than absolute. Rna 4:626-38.

[125] Katz, R. A. and Skalka, A. M. (1990). Generation of diversity in retroviruses. Ann. Rev. Genet., 24:409-445.

[126] Kaye, J. F. & Lever, A. M. (1996). trans-acting proteins involved in RNA encapsidation and viral assembly in human immunodeficiency virus type 1. J. Virol. 70:880-6.

[127] Kaye, J. F. & Lever, A. M. (1999). Human immunodeficiency virus types 1 and 2 differ in the predominant mechanism used for selection of genomic RNA for encapsidation. J Virol 73, 3023-

[128] Konings, D., Nash M., Maizel J. and Arlinghaus R. (1992). Novel GACG-hairpin pair motif in the 5' untranslated region of type C retroviruses related to murine leukemia virus. J. Virol. 66:632-640.

[129] Lapadat-Tapolsky, M., de Rocquigny, H., van Gent, D., Roques, B., Plasterk, R. and Darlix, J.-L. (1993). Interactions between HIV-1 nucleocapsid protein and viral DNA may have important functions in the viral life cycle. Nucleic Acids Res. 21:831-839.

[130] Lapadat-Tapolsky, M., Pernelle, C., Borie, C. and Darlix, J.-L. (1995). Analysis of the nucleic acid annealing activities of nucleocapsid protein from HIV-1. Nucleic Acids Res. 23:2434-2441.

[131] Lapadat-Tapolsky M, Gabus C, Rau M, Darlix JL. (1997). Possible roles of HIV-1 nucleocapsid protein in the specificity of proviral DNA synthesis and in its variability. J. Mol. Biol. 268(2):250-260.

[132] Laughrea M, Jette L, Mak J, Kleiman L, Liang C, Wainberg MA. (1997). Mutations in the kissing-loop hairpin of human immunodeficiency virus type 1 reduce viral infectivity as well as genomic RNA packaging and dimerization. J. Virol. 71:3397-406.

[133] Lener, D., Tanchou, V., Roques, BP, Le Grice S., and Darlix, JL. (1998). Involvement of HIV-1 NC protein in the recruitment of RT into nucleoprotein complexes formed in vitro. J. Biol. Chem. 273, 33781-33786 .

[134] Lever, A., Göttlinger, Haseltine, W. and Sodroski, J. (1989). Identification of a sequence required for efficient packaging of HIV-1 RNA into virions. J. Virol. 63:4085-4087.

[135] Levin JG, Rosenak MJ. (1976). Synthesis of murine leukemia virus proteins associated with virions assembled in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Proc. Natl. Acad. Sci. USA 73(4):1154-1158.

[136] Levy, D. N., Fernandes, L. S., Williams, W. V. & Weiner, D. B. (1993). Induction of cell differentiation by human immunodeficiency virus 1 vpr. Cell 72:541-50.

[137] Liang, C., Hu, J., Russell, R. S. & Wainberg, M. A. (2002). Translation of Pr55(gag) augments packaging of human immunodeficiency virus type 1 RNA in a cis-acting manner. AIDS Res. Hum. Retroviruses 18:1117-26.

[138] Lopez-Lastra, M., Gabus, C. & Darlix, J. L. (1997). Characterization of an internal ribosomal entry segment within the 5' leader of avian reticuloendotheliosis virus type A RNA and development of novel MLV-REV-based retroviral vectors. Hum Gene Ther 8:1855-65.

[139] Lopez-Lastra, M., Ulrici, S., Gabus, C. & Darlix, J. L. (1999). Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors. J. Virol. 73:8393-402.

[140] Lori, F., Veronese, F., Devico, A., Lusso, P., Reitz, M., and Gallo, R. (1992). Viral DNA carried by HIV-1 virions. J. Virol. 66:5067-5074.

[141] Luban, J. & Goff, S. P. (1991). Binding of human immunodeficiency virus type 1 (HIV-1) RNA to recombinant HIV-1 gag polyprotein. J. Virol. 65:3203-12.

[142] Maki, A. H., Ozarowski, A., Misra, A., Urbaneja, M. A. & Casas-Finet, J. R. (2001). Phosphorescence and optically detected magnetic resonance of HIV-1 nucleocapsid protein complexes with stem-loop sequences of the genomic Psi-recognition element. Biochemistry 40:1403-12.

[143] McBride, M. S. & Panganiban, A. T. (1996). The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures. J. Virol. 70:2963-73.

[144] McCarthy, M. (1995). HIV gene arrests cell cycle. Lancet 346, 960.

[145] McGhee, J. D. & von Hippel, P. H. (1974). Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J. Mol. Biol. 86:469-89.

[146] Mély, Y., De Rocquigny, H., Morellet, N., Roques, B. P. & Gérard, D. (1996). Zinc binding to the HIV-1 nucleocapsid protein: a thermodynamic investigation by fluorescence spectroscopy. Biochemistry 35:5175-5182.

[147] Méric, C., Darlix, J. L. and Spahr, P. F. (1984). It is Rous sarcoma virus protein p12 and not p19 that binds tightly to Rous sarcoma virus RNA. J. Mol. Biol. 173:531-538.

[148] Méric, C. & Spahr, P. F. (1986). Rous sarcoma virus nucleic acid binding protein p12 is necessary for viral 70S RNA dimer formation and packaging. J. Virol. 60:450-459.

[149] Méric, C. & Goff, S. (1989) Characterization of Moloney murine leukemia virus mutants with single amino-acid substitutions in the Cys-His box of the nucleocapsid protein. J. Virol. 63:1558-1568.

[150] Morellet N, Demene H, Teilleux V, Huynh-Dinh T, de Rocquigny H, Fournie-Zaluski MC, Roques BP.(1998) Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the single-stranded pentanucleotide d(ACGCC). J Mol Biol. 283(2):419-34

[151] Morellet, N., de Rocquigny, H., Mély, Y., Jullian, N., Deméné, H., Ottmann, M., Gérard, D., Darlix, J-L, Fournié-Zaluski, M-C., Roques, B. (1994). Conformational behaviour of the active and inactive forms of the nucleocapsid NCp7 of HIV-1 studied by 1H-NMR. J. Mol. Biol. 235:287-301.

[152] Mouland, A. J., Coady, M., Yao, X. J. & Cohen, E. A. (2002). Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression. Virology 292:321-30.

[153] Mujeeb, A., Clever, J. L., Billeci, T. M., James, T. L. & Parslow, T. G. (1998). Structure of the dimer initiation complex of HIV-1 genomic RNA. Nat Struct Biol 5:432-6.

[154] Muriaux, D., De Rocquigny, H., Roques, B. P. & Paoletti, J. (1996). NCp7 activates HIV-1Lai RNA dimerization by converting a transient loop-loop complex into a stable dimer. J. Biol. Chem. 271:33686-92.

[155] Muriaux D, Mirro J, Nagashima K, Harvin D, Rein A. (2002) Murine leukemia virus nucleocapsid mutant particles lacking viral RNA encapsidate ribosomes. J Virol. 76(22):11405-11413.

[156] Muriaux D, Mirro J, Harvin D, Rein A. (2001). RNA is a structural element in retrovirus particles. Proc. Natl. Acad. Sci. USA 98(9):5246-5251.

[157] Nanbru, C., Prats, A. C., Droogmans, L., Defrance, P., Huez, G. & Kruys, V. (2001). Translation of the human c-myc P0 tricistronic mRNA involves two independent internal ribosome entry sites. Oncogene 20:4270-80.

[158] Negroni M, Buc H. (2002). Mechanisms of retroviral recombination. Annu Rev Genet. 2001;35:275-302.

[159] Nissen-Meyer, J. and Abraham, A. (1980). Specificity of RNA binding by the structural protein (p10) of F-MuLV. J. Mol. Biol. 142:19-28.

[160] Oertle, S. & Spahr, P. F. (1990). Role of the Gag polyprotein precursor in packaging and maturation of Rous sarcoma virus genomic RNA. J. Virol. 64:5757-5763.

[161] Ohlmann, T., Lopez-Lastra, M. & Darlix, J. L. (2000). An internal ribosome entry segment promotes translation of the simian immunodeficiency virus genomic RNA. J. Biol. Chem. 275:11899-906.

[162] Ottmann, M. Gabus, C. and Darlix, J-L. (1995) The central globular domain of the nucleocapsid protein of HIV-1 is critical for virion structure and infectivity. J. Virol. 69:1778-1784.

[163] Pager, J., Coulaud, D. and Delain, E. (1994). Electron microscopy of the nucleocapsid from disrupted MoMuLV and of associated type VI collagen-like filaments. J. Virol. 68:223-232.

[164] Paillart, J.-C., Marquet, R., Skripkin, E., Ehresmann, B. & Ehresmann, C. (1994). Mutational analysis of the bipartite dimer linkage structure of HIV-1 genomic RNA. J. Biol. Chem. 269:27486-27493.

[165] Paillart JC, Berthoux L, Ottmann M, Darlix JL, Marquet R, Ehresmann B, Ehresmann C. (1996). A dual role of the putative RNA dimerization initiation site of human immunodeficiency virus type 1 in genomic RNA packaging and proviral DNA synthesis. J. Virol. 70:8348-54.

[166] Paoletti, A. C., Shubsda, M. F., Hudson, B. S. & Borer, P. N. (2002). Affinities of the nucleocapsid protein for variants of SL3 RNA in HIV-1. Biochemistry 41:15423-8.

[167] Parkin, N. T., Cohen, E. A., Darveau, A., Rosen, C., Haseltine, W. & Sonenberg, N. (1988). Mutational analysis of the 5' non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation. Embo J 7:2831-7.

[168] Pestova, T. V., Hellen, C. U. & Shatsky, I. N. (1996). Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry. Mol Cell Biol 16:6859-69.

[169] Pestova, T. V., Shatsky, I. N. & Hellen, C. U. (1996). Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes. Mol Cell Biol 16:6870-8.

[170] Poznansky, M., Lever, A., Bergeron, L., Haseltine, W. & Sodroski, J. (1991). Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector. J. Virol. 65:532-6.

[171] Prats, A.-C., Housset, V., de Billy, G., Cornille, F., Prats, H., Roques, B. and Darlix, J.-L. (1991). Viral annealing activity of the nucleocapsid protein of MoMuLV is zinc independent. Nucleic Acids Res. 13:3533-3541.

[172] Prats, A.-C., Sarih, L., Gabus, C., Litvak, S., Keith, G. and Darlix, J.-L. (1988). Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. EMBO J., 7:1777-1783.

[173] Pyronnet, S., Pradayrol, L. & Sonenberg, N. (2000). A cell cycle-dependent internal ribosome entry site. Mol Cell Biol 5:607-16.

[174] Pyronnet, S., Dostie, J. & Sonenberg, N. (2001). Suppression of cap-dependent translation in mitosis. Genes Dev 15:2083-93.

[175] Pyronnet, S. & Sonenberg, N. (2001). Cell-cycle-dependent translational control. Curr Opin Genet Dev 11:13-8.

[176] Rabson, A. B. & Graves, B. J. (1997). Synthesis and processing of viral RNA. In Retroviruses (Coffin, J. M., Hughes, S. M. & Varmus, H. E., eds.), pp. 205. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

[177] Ramboarina, S., Druillennec, S., Morellet, N., Bouaziz, S. & Roques, B. P. (2003). Structural role of the first zinc knuckle of the HIV-1 NCp7 investigated by NMR and biochemical studies of the Cys28-His mutant. J. Virol., submitted.

[178] Ramboarina, S., Srividya, R. A., Atkinson, R. A., Morellet, N., Roques, B. P., J.-F. Lefèvre, Mély, Y. and Kieffer, B. (2002) Effects of temperature on the dynamic behaviour of the HIV1 nucleocapsid NCp7 and its DNA complex. J. Mol. Biol., 316(3), 611-627.

[179] Re, F., Braaten, D., Franke, E. K. & Luban, J. (1995). Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J. Virol. 69:6859-64.

[180] Rein, A., Henderson, L. E. & Levin, J. G. (1998). Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance for viral replication. Trends Biochem Sci 23:297-301.

[181] Rémy, E., H. de Rocquigy, H., Petitjean, P., Muriaux, D., Teilleux, V., Paoletti, J. & Roques, B. P. (1998). The anneling of tRNALys,3 to human immunodeficiency virus type 1 primer binding site is critically dependent on the NCp7 zinc fingers structure. J. Biol. Chem. 273(9), 4819-4822.

[182] Rice, W., Schaeffer, C., Graham, L., et al., (1993). The site of antiviral action of 3-nitrosobenzamide on the infectivity process of HIV in human lymphocytes. Proc. Natl. Acad. Sci USA 90:9721-9724.

[183] Ricchetti, M. and Buc, H. (1990) Reverse transcriptases and genomic variability: the accuracy of DNA replication is enzyme specific and sequence dependent. EMBO J., 9:1583-1593.

[184] Richardson, J. H., Child, L. A. & Lever, A. M. (1993). Packaging of human immunodeficiency virus type 1 RNA requires cis-acting sequences outside the 5' leader region. J. Virol. 67:3997-4005.

[185] Rist, M. J. & Marino, J. P. (2002). Mechanism of nucleocapsid protein catalyzed structural isomerization of the dimerization initiation site of HIV-1. Biochemistry 41:14762-70.

[186] Roberts, L. O., Seamons, R. A. & Belsham, G. J. (1998). Recognition of picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. Rna 4:520-529.

[187] Roda RH, Balakrishnan M, Kim JK, Roques BP, Fay PJ, Bambara R. (2002) Strand transfer occurs in retroviruses by a pause-initiated two-step mechanism. J Biol Chem. 277(49):46900-46911.

[188] Rodriguez-Rodriguez L, Tsuchihashi Z, Fuentes GM, Bambara RA, Fay PJ . (1995) Influence of human immunodeficiency virus nucleocapsid protein on synthesis and strand transfer by the reverse transcriptase in vitro. J. Biol. Chem. 270(25):15005-15011.

[189] Rous, P. (1910) A transmissible avian neoplasm : sarcoma of the common fowl. J. Exp. Med. 12:696-705.

[190] Sachs, A. B. (2000). Cell cycle-dependent translation initiation: IRES elements prevail. Cell 101:243-245.

[191] Sakagushi, K., Zambrano, N., Baldwin, E. T. et al. Identification of a binding site for the human immunodeficiency virus type 1 nucleocapsid protein. Proc. Natl. Acad. Sci. USA 1993, 90:5219-23.

[192] Sarkar, N., Nowinski, R. and Moore, D. (1971). Helical nucleocapsid structure of the oncogenic ribonucleic acid viruses (oncornaviruses). J. Virol. 8:564-572.

[193] Schulein, M., Burnette, W. and August, T. (1978). Stoichiometry and specificity of binding of Rauscher Oncovirus p10 structural protein to nucleic acids. J. Virol. 26:54-60.

[194] Sen, A. and Todaro, G. (1977). The genome associated, specific RNA binding proteins of avian and mammalian type C viruses. Cell 10:91-99.

[195] Skripkin E, Paillart JC, Marquet R, Ehresmann B, Ehresmann C. (1994). Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro. Proc. Natl. Acad. Sci. USA 91:4945-4949.

[196] Shubsda, M. F., Paoletti, A. C., Hudson, B. S. & Borer, P. N. (2002). Affinities of packaging domain loops in HIV-1 RNA for the nucleocapsid protein. Biochemistry 41:5276-82.

[197] Shubsda, M. F., Kirk, C. A., Goodisman, J. & Dabrowiak, J. C. (2000). Binding of human immunodeficiency virus type 1 nucleocapsid protein to psi-RNA-SL3. Biophys Chem 87:149-65.

[198] Smith, B. & Bailey, J. (1979). The binding of an avian myeloblastosis virus basic 12 000 dalton protein to nucleic acids. Nucl. Acids Res. 7:2055-2072.

[199] Sonstegard, T. S. & Hackett, P. B. (1996). Autogenous regulation of RNA translation and packaging by Rous sarcoma virus Pr76gag. J. Virol. 70:6642-52.

[200] Stoltzfus, M. and Snyder, P. (1975). Structure of B77 sarcoma virus RNA: stabilization of RNA after packaging. J. Virol. 16:1161-1170.

[201] Summers, M. F., South, T. L., Kim, B., Hare, D. R. High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. Biochemistry 1990, 29:329-40.

[202] Svitkin, Y. V., Pause, A. & Sonenberg, N. (1994). La autoantigen alleviates translational repression by the 5' leader sequence of the human immunodeficiency virus type 1 mRNA. J. Virol. 68:7001-7.

[203] Tanchou, V., Gabus, C., Rogemond, V. and Darlix, J.-L. (1995). Formation of stable and functional HIV-1 nucleoprotein complexes in vitro. J. Mol. Biol. 252:563-571.

[204] Temin, H. & Mizutani, S. (1970). RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211-1213.

[205] Temin, H. (1991). Sex and recombination in retroviruses. TIG 7:71-74.

[206] Theilleux-Delalande, V., Girard, F., Huynh-Dinh, T., Lancelot, G. & Paoletti, J. (2000). The HIV-1(Lai) RNA dimerization. Thermodynamic parameters associated with the transition from the kissing complex to the extended dimer. Eur J Biochem 267:2711-2719.

[207] Tisné, C., Roques, B. P. & Dardel, F. (2001). Heteronuclear NMR studies of the interaction of tRNALys,3 with HIV-1 nucleocapsid protein. J. Mol. Biol., 306(3), 443-454.

[208] Trono D. (1992). Partial reverse transcripts in virions from human immunodeficiency and murine leukemia viruses. J Virol. 66:4893-4900.

[209] Tsuchihashi, Z. and Brown, P. O. (1994). DNA strand exchange and selective DNA annealing promoted by the human immunodeficiency virus type 1 nucleocapsid protein. J. Virol., 68:5863-5870.

[210] Vagner, S., Waysbort, A., Marenda, M., Gensac, M. C., Amalric, F. & Prats, A. C. (1995). Alternative translation initiation of the Moloney murine leukemia virus mRNA controlled by internal ribosome entry involving the p57/PTB splicing factor. J. Biol. Chem. 270:20376-83.

[211] Vuilleumier, C., Bombarda, E., Morellet, N., Gerard, D., Roques, B. P. & Mely, Y. (1999). Nucleic acid sequence discrimination by the HIV-1 nucleocapsid protein NCp7: a fluorescence study. Biochemistry 38:16816-25.

[212] Wilson, J. E., Powell, M. J., Hoover, S. E. & Sarnow, P. (2000). Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites. Mol Cell Biol 20:4990-9.

[213] Yang, S. and Temin, H. (1994). A double hairpin structure is necessary for the efficient encapsidation of spleen necrosis virus retroviral RNA. EMBO J. 13:713-726.

[214] You, J-C. and McHenry, C. S. (1994). HIV nucleocapsid protein accelerates strand transfer of the terminally redundant sequences involved in reverse transcription. J. Biol. Chem. 269:31491-31495.

[215] Yu, Q. and Darlix, J-L. (1996). The Zinc finger of nucleocapsid protein of Friend MuLV is critical for proviral DNA synthesis in vivo. J. Virol. 70:5791-5798.

[216] Zack JA, Haislip AM, Krogstad P, Chen I. (1992). Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J. Virol. 66:1717-1725.

[217] Zeffman, A., Hassard, S., Varani, G. & Lever, A. (2000). The major HIV-1 packaging signal is an extended bulged stem loop whose structure is altered on interaction with the Gag polyprotein. J. Mol. Biol. 297:877-93.

[218] Zhang, H., Basgara, O., Niikura, M., Poiesz, B. and Pomerantz, R. (1994). Intravirion reverse transcripts in the peripheral blood plasma of HIV-1 infected individuals. J. Virol. 68:7591-7597.

[219] Zhou, W., Parent, L., Wills, J. and Resh, M. (1994). Identification of a membrane binding domain within the amino-terminal region of HIV-1 gag protein which interacts with acidic phospholipids. J. Virol. 68:2556-2569.

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