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Coreceptor Use by Primate Lentiviruses


Christopher C. Broder and Agnes Jones-Trower

Department of Microbiology and Immunology, F. Edward Hébert School of Medicine
Uniformed Services University of the Health Sciences
4301 Jones Bridge Road, Bethesda, MD 20814-4799
Phone: 301-295-3401, Fax: 301-295-1545, email:


The original compilation of the data in the accompanying tables in this section on coreceptor use by HIV-1, HIV-2, and SIV was performed over the past two years by Robert W. Doms and Aimee L. Edinger of the University of Pennsylvania, Department of Pathology and Laboratory Medicine and John P. Moore of The Aaron Diamond AIDS Research Center, The Rockefeller University. This year we have updated and revised the information in these tables for the purpose of maintaining this database on the salient points of virus isolate characteristics and usage of these seven transmembrane domain (7TM) coreceptors. In addition, we have included all HIV-1 isolates and their relevant information from the NIH AIDS Research and Reference Reagent Program that were not already in the existing HIV-1 isolate table. The coreceptor usage data included in this review is included as a searchable field for HIV sequence retrieval at the HIV database web site, Corrections to errors or additional information that would improve these tables are welcome and should be sent by electronic mail to: .

HIV-1 Table

NIH Reagent Table

HIV-2 Table

SIV Table


Parallel tracks of HIV research began almost simultaneously in two very different arenas, namely immunology and virology. One field focused on the structural and functional characterization of how HIV-1 entered a host cell, with the goal of teasing out the steps and requirements for infection, whereas the other line of research endeavored to define host factors capable of inhibiting HIV-1 replication. For over a decade these lines of research continued but remained essentially separated. Their findings individually built-up our understanding of the biology of HIV until crossovers occurred, shedding light on at least two long-standing unknowns about the virus: (i) some soluble suppressive factors are chemokines and (ii) the tropism-determining/influencing coreceptors for virus entry are chemokine receptors.

A significant part of the overall modulation of HIV-1 replication and the progress of HIV-1-induced disease occurs via a balance of host factors Fauci96,Levy98. Some of these factors, such as pro-inflammatory cytokines and cellular activation, stimulate viral replication while other inhibitory factors may counteract disease progression. The ligands for the chemokine receptors being utilized as coreceptors for HIV-1 entry and infection are the newly discovered suppressive factors. Further, it has long been noted that there is a temporal change in viral tropism during the course of HIV-1 infection as related to the switch from NSI to SI phenotype and, for the most part, can now be correlated to the specific use of different coreceptors. This switch could be related to colonization of different types of cells rather than escape from immune system pressure. It has been proposed that the antigenic diversity of the HIV-1 envelope glycoprotein could be primarily driven by adaptation to new coreceptors and only secondarily by immune selection Weiss96 based on these observations: the properties of the HIV-1 coreceptors; the diversity of retrovirus receptors; and the availability of numerous seven transmembrane domain receptors on cell surfaces. It has also been suggested that during the long infection period, the HIV-1 quasispecies has the opportunity to colonize new cell types, thus gradually invading different subsets of hematopoietic and brain cells Weiss96. Of further interest, it has also been observed that feline immunodeficiency virus (FIV) can use CXCR4 to infect and fuse in a CD4-independent manner Willett97. It appears that chemokine receptors could be a common link between FIV and the primate lentiviruses Willett97. It is tempting to speculate that chemokine receptors (or other multiple membrane spanning receptors) were originally used as primary (and possibly exclusive) receptors by lentiviruses, and that the adaptation to use CD4 was a later event (a notion first proposed by R. Weiss).

Other retroviruses do utilize various multiple membrane-spanning domain proteins (reviewed in Weiss93,Weiss95). It was previously proposed that perhaps HIV-1 has developed a dependence on CD4 and CXCR4 or CCR5 because the CD4 and the 7TM receptor(s) are co-localized in the cell membrane Broder96. It may be that CD4 and certain 7TM receptors have some functional interacting role in the cells of the immune system. Indeed, a constitutive association between the CD4 and CCR5 receptors has recently been demonstrated, Xiao99 and this observation may also explain why macrophages expressing CXCR4 and CCR5 are predominately only a target for M-tropic isolates of HIV-1 Dimitrov99. In fact, the involvement of a 7TM protein in HIV-1 infection was postulated in 1995 by W. Gallaher, Gallaher95 in the context of a 'multiple receptor' requirement. Based on the utilization by ecotropic murine leukemia virus of a multiple membrane spanning receptor (but in fact a 14 TM rather than 7TM glycoprotein) Albritton89 they proposed a structural model in which multiple domains of the gp120 subunit of the envelope glycoprotein would interact with a 7TM host cell molecule in addition to CD4.

Continued progress over the past year has been made detailing coreceptor usage for HIV-1, HIV-2, and SIV strains, and in describing new virus isolates along with their salient features. It was previously proposed that perhaps HIV-1 has developed a dependence on CD4 and CCR5 or CXCR4 because the CD4 and the 7TM receptor(s) are co-localized in the cell membrane Broder96. Indeed, it may be that CD4 and certain 7TM receptors have some, yet to be discovered, functional interacting role in the cells of the immune system. In fact, a constitutive biochemical association between the CD4 and CCR5 receptors which supports such a model has recently been demonstrated Xiao99. On the other hand, the endogenous association between CD4 and the CXCR4 coreceptor appears much weaker and is more easily measured only after complexed with HIV-1 gp120 Lapham96,Dimitrov99. The observation that the CCR5-CD4 interaction is stronger than the CXCR4-CD4 interaction may also explain why macrophages expressing both these coreceptors are predominately only a target for M-tropic isolates of HIV-1 Dimitrov99. In addition, the important observations of coreceptor use by several virus isolates in the absence of CD4 have suggested new hypotheses concerning the evolution of HIV-1, HIV-2 and SIV, the mechanism of the receptor-induced membrane fusion process, and the structure of the coreceptor molecules. The number of coreceptors used by HIV and SIV is now 14 (CCR5, CXCR4, CCR3, CCR2b, STRL33 (Bonzo), GPR1, GPR15 (BOB), CCR8, CCR9, CCR1, CCR4, CX3CR1 (formerly V28), APJ and US28). This number does not include non-human analogues (other than US28) and is likely to grow. However, it is now well recognized that the principal HIV-1 coreceptors remain the initially discovered CXC chemokine receptor CXCR4 and the CC-chemokine receptor CCR5, and all HIV-1, HIV-2, and SIV strains reported on to date use one or both of these receptors. Unlike HIV-1, it appears that many isolates of HIV-2 and SIV have the added ability to employ alternate coreceptors with efficiencies comparable to that with either CXCR4 or CCR5 depending on the particular isolate, and some can employ the coreceptor in the absence of CD4. It remains an open question as to whether use of alternative coreceptors in vivo is an important feature in viral tropism, pathogenesis or other facets of the natural history of these viruses. Indeed, the use of alternate coreceptors other than CCR5 or CXCR4, or their use in a CD4-independent manner, could enable particular virus strains to engage new cellular targets in vivo. There have been numerous reviews published on the subject of HIV/SIV and the coreceptors since 1996 which serve as the best source of detailed information and citations for readers of these tables. Broder96, Moore97a, Broder97, Dimitrov97, Doranz97, Dimitrov98, Berson98, Gabuzda98, Rucker98, Berger99, Clapham99, Edinger99b, Hoffman99, Michael99, Kalinkovich99, Ross99, Lee99 These new data concerning the cellular coreceptors for HIV and the natural chemokine ligands for those receptors continues to advance our understanding of HIV pathogenesis and has offered new therapeutic and preventive strategies.

The coreceptor use tables are updated from last year. The major coreceptor(s) used by each virus strain is listed, as are alternative coreceptors that support virus infection in vitro to an extent that is ~10% of the efficiency of the major coreceptor used by each virus strain.


[Albert87] J. Albert, U. Bredberg, F. Chiodi, B. Bottiger, E. M. Fenyo, E. Norrby, G. Biberfeld, A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II, and HTLV-IIIB, AIDS Res Hum Retroviruses,3:3-10 (1987).

[Alkhatib96] G. Alkhatib, C. Combadiere, C. C. Broder, Y. Feng, P. E. Kennedy, P. M. Murphy, E. A. Berger, CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1, Science,272:1955-8 (1996).

[Amedee95] A. M. Amedee, N. Lacour, J. L. Gierman, L. N. Martin, J. E. Clements, R. Bohm, R. M. Harrison, M. Murphey-Corb, Genotypic selection of simian immunodeficiency virus in macaque infants infected transplacentally, J Virol,69:7982-90 (1995).

[Balotta97] C. Balotta, P. Bagnarelli, M. Violin, A. L. Ridolfo, D. Zhou, A. Berlusconi, S. Corvasce, M. Corbellino, M. Clementi, M. Clerici, M. Moroni, M. Galli, Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient, AIDS,11:F67-71 (1997).

[Banapour91a] B. Banapour, M. L. Marthas, R. J. Munn, P. A. Luciw, In vitro macrophage tropism of pathogenic and nonpathogenic molecular clones of simian immunodeficiency virus (SIVmac), Virology,183:12-9 (1991).

[Banapour91b] B. Banapour, M. L. Marthas, R. A. Ramos, B. L. Lohman, R. E. Unger, M. B. Gardner, N. C. Pedersen, P. A. Luciw, Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac, J Virol,65:5798-805 (1991).

[Barnett96] S. W. Barnett, H. S. Legg, Y. Sun, J. Klinger, D. J. Blackbourn, C. P. Locher, J. A. Levy, Molecular cloning of the human immunodeficiency virus subtype 2 strain HIV-2UC2, Virology,222:257-61 (1996).

[Bazan98] H. A. Bazan, G. Alkhatib, C. C. Broder, E. A. Berger, Patterns of CCR5, CXCR4, and CCR3 usage by envelope glycoproteins from human immunodeficiency virus type 1 primary isolates, J Virol,72:4485-91 (1998).

[Berger97a] E. A. Berger, HIV1 entry and tropism: the chemokine receptor connection, AIDS,11 (supplement A):S3-S16 (1997).

[Berger97b] E. A. Berger, R. W. Doms, E.-M. Fenyo, B. T. M. Korber, D. R. Littman, J. P. Moore, Q. J. Sattentau, H. Schuitmaker, J. Sodroski, R. A. Weiss, HIV-1 phenotypes classified by coreceptor usage, Nature,In press: (1997).

[Biti97] R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, T. Liang, HIV-1 infection in an individual homozygous for the CCR5 deletion allele (letter; comment), Nat Med,3:252-3 (1997).

[Bjorndal97] A. Bjorndal, H. Deng, M. Jansson, J. R. Fiore, C. Colognesi, A. Karlsson, J. Albert, G. Scarlatti, D. R. Littman, E. M. Fenyo, Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype, J Virol,71:7478-87 (1997).

[Brelot97] A. Brelot, N. Heveker, O. Pleskoff, N. Sol, M. Alizon, Role of the first and third extracellular domains of CXCR-4 in human immunodeficiency virus coreceptor activity, J Virol,71:4744-51 (1997).

[Broder97] C. C. Broder, R. G. Collman, Chemokine receptors and HIV, J Leukoc Biol,62:20-9 (1997).

[Bron97] R. Bron, P. J. Klasse, D. Wilkinson, P. R. Clapham, A. Pelchen-Matthews, C. Power, T. N. Wells, J. Kim, S. C. Peiper, J. A. Hoxie, M. Marsh, Promiscuous use of CC and CXC chemokine receptors in cell-to-cell fusion mediated by a human immunodeficiency virus type 2 envelope protein, J Virol,71:8405-15 (1997).

[Chackerian97] B. Chackerian, E. M. Long, P. A. Luciw, J. Overbaugh, Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection, J Virol,71:3932-9 (1997).

[Chakrabarti90] S. Chakrabarti, T. Mizukami, G. Franchini, B. Moss, Synthesis, oligomerization, and biological activity of the human immunodeficiency virus type 2 envelope glycoprotein expressed by a recombinant vaccinia virus, Virology,178:134-42 (1990).

[Chen97] Z. Chen, P. Zhou, D. D. Ho, N. R. Landau, P. A. Marx, Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry, J Virol,71:2705-14 (1997).

[Chen98a] Z. Chen, A. Gettie, D. D. Ho, P. A. Marx, Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2, and SIVmac, Virology,246:113-24 (1998).

[Chen98b] Z. Chen, D. Kwon, Z. Jin, S. Monard, P. Telfer, M. S. Jones, C. Y. Lu, R. F. Aguilar, D. D. Ho, P. A. Marx, Natural infection of a homozygous delta24 CCR5 red-capped mangabey with an R2b-tropic simian immunodeficiency virus, J Exp Med,188:2057-65 (1998).

[Choe96] H. Choe, M. Farzan, Y. Sun, N. Sullivan, B. Rollins, P. D. Ponath, L. Wu, C. R. Mackay, G. LaRosa, W. Newman, N. Gerard, C. Gerard, J. Sodroski, The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates, Cell,85:1135-48 (1996).

[Choe98] H. Choe, M. Farzan, M. Konkel, K. Martin, Y. Sun, L. Marcon, M. Cayabyab, M. Berman, M. E. Dorf, N. Gerard, C. Gerard, J. Sodroski, The orphan seven-transmembrane receptor apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1, J Virol,72:6113-8 (1998).

[Clapham92] P. R. Clapham, A. McKnight, R. A. Weiss, Human immunodeficiency virus type 2 infection and fusion of CD4- negative human cell lines: induction and enhancement by soluble CD4, J Virol,66:3531-7 (1992).

[Clavel86] F. Clavel, D. Guetard, F. Brun-Vezinet, S. Chamaret, M. A. Rey, M. O. Santos-Ferreira, A. G. Laurent, C. Dauguet, C. Katlama, C. Rouzioux, Isolation of a new human retrovirus from West African patients with AIDS, Science,233:343-6 (1986).

[Collman92] R. Collman, J. W. Balliet, S. A. Gregory, H. Friedman, D. L. Kolson, N. Nathanson, A. Srinivasan, An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1, J Virol,66:7517-21 (1992).

[Connor93] R. I. Connor, H. Mohri, Y. Cao, D. D. Ho, Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals, J Virol,67:1772-7 (1993).

[Dean96] M. Dean, M. Carrington, C. Winkler, G. A. Huttley, M. W. Smith, R. Allikmets, J. J. Goedert, S. P. Buchbinder, E. Vittinghoff, E. Gomperts, S. Donfield, D. Vlahov, R. Kaslow, A. Saah, C. Rinaldo, R. Detels, S. J. O'Brien, Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study (see comments) (published erratum appears in Science 1996 Nov 15;274(5290):1069), Science,273:1856-62 (1996).

[DeJong92] J. J. de Jong, J. Goudsmit, W. Keulen, B. Klaver, W. Krone, M. Tersmette, A. de Ronde, Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity, J Virol,66:757-65 (1992).

[Deng97] H. K. Deng, D. Unutmaz, V. N. KewalRamani, D. R. Littman, Expression cloning of new receptors used by simian and human immunodeficiency viruses (see comments), Nature,388:296-300 (1997).

[Dittmar97] M. T. Dittmar, G. Simmons, S. Hibbitts, M. O'Hare, S. Louisirirotchanakul, S. Beddows, J. Weber, P. R. Clapham, R. A. Weiss, Langerhans cell tropism of human immunodeficiency virus type 1 subtype A through F isolates derived from different transmission groups, J Virol,71:8008-13 (1997).

[Doms97] R. W. Doms, S. C. Peiper, Unwelcomed guests with master keys: how HIV uses chemokine receptors for cellular entry, Virology,235:179-90 (1997).

[Doranz96] B. J. Doranz, J. Rucker, Y. Yi, R. J. Smyth, M. Samson, S. C. Peiper, M. Parmentier, R. G. Collman, R. W. Doms, A dual-tropic primary HIV-1 isolate that uses fusin and the beta- chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors, Cell,85:1149-58 (1996).

[Dragic96] T. Dragic, V. Litwin, G. P. Allaway, S. R. Martin, Y. Huang, K. A. Nagashima, C. Cayanan, P. J. Maddon, R. A. Koup, J. P. Moore, W. A. Paxton, HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC- CKR-5 (see comments), Nature,381:667-73 (1996).

[Edinger97a] A. L. Edinger, A. Amedee, K. Miller, B. J. Doranz, M. Endres, M. Sharron, M. Samson, Z. H. Lu, J. E. Clements, M. Murphey-Corb, S. C. Peiper, M. Parmentier, C. C. Broder, R. W. Doms, Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains, Proc Natl Acad Sci U S A,94:4005-10 (1997).

[Edinger97b] A. L. Edinger, J. L. Mankowski, B. J. Doranz, B. J. Margulies, B. Lee, J. Rucker, M. Sharron, T. L. Hoffman, J. F. Berson, M. C. Zink, V. M. Hirsch, J. E. Clements, R. W. Doms, CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain, Proc Natl Acad Sci U S A,94:14742-7 (1997).

[Edinger98a] A. L. Edinger, T. L. Hoffman, M. Sharron, B. Lee, B. O'Dowd, R. W. Doms, Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins, Virology,249:367-78 (1998).

[Edinger98b] A. L. Edinger, T. L. Hoffman, M. Sharron, B. Lee, Y. Yi, W. Choe, D. L. Kolson, B. Mitrovic, Y. Zhou, D. Faulds, R. G. Collman, J. Hesselgesser, R. Horuk, R. W. Doms, An orphan seven-transmembrane domain receptor expressed widely in the brain functions as a coreceptor for human immunodeficiency virus type 1 and simian immunodeficiency virus, J Virol,72:7934-40 (1998).

[Edingersubmit] A. L. Edinger, C. Blanpain, K. Kunstman, S. M. Wolinsky, M. Endres, M. Parmentier, R. W. Doms, Functional dissection of CCR5 coreceptor function through the use of CD4-independent SIV strains, ,: (1999).

[Endres96] M. J. Endres, P. R. Clapham, M. Marsh, M. Ahuja, J. D. Turner, A. McKnight, J. F. Thomas, B. Stoebenau-Haggarty, S. Choe, P. J. Vance, T. N. Wells, C. A. Power, S. S. Sutterwala, R. W. Doms, N. R. Landau, J. A. Hoxie, CD4-independent infection by HIV-2 is mediated by fusin/CXCR4, Cell,87:745-56 (1996).

[Evans88] L. A. Evans, J. Moreau, K. Odehouri, D. Seto, G. Thomson-Honnebier, H. Legg, A. Barboza, C. Cheng-Mayer, J. A. Levy, Simultaneous isolation of HIV-1 and HIV-2 from an AIDS patient, Lancet,2:1389-91 (1988).

[Farzan97] M. Farzan, H. Choe, K. Martin, L. Marcon, W. Hofmann, G. Karlsson, Y. Sun, P. Barrett, N. March, , N. Sullivan, N. Gerard, C. Gerard, J. Sodroski, Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection, J Exp Med.,186:405-11 (1997).

[Feng96] Y. Feng, C. C. Broder, P. E. Kennedy, E. A. Berger, HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor (see comments), Science,272:872-7 (1996).

[Fenyo88] E. M. Fenyo, L. Morfeldt-Manson, F. Chiodi, B. Lind, A. von Gegerfelt, J. Albert, E. Olausson, B. Asjo, Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates, J Virol,62:4414-9 (1988).

[Flaherty97] M. T. Flaherty, D. A. Hauer, J. L. Mankowski, M. C. Zink, J. E. Clements, Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus, J Virol,71:5790-8 (1997).

[Fouchier92] R. A. Fouchier, M. Groenink, N. A. Kootstra, M. Tersmette, H. G. Huisman, F. Miedema, H. Schuitemaker, Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule, J Virol,66:3183-7 (1992).

[Gao92] F. Gao, L. Yue, A. T. White, P. G. Pappas, J. Barchue, A. P. Hanson, B. M. Greene, P. M. Sharp, G. M. Shaw, B. H. Hahn, Human infection by genetically diverse SIVSM-related HIV-2 in west Africa, Nature,358:495-9 (1992).

[Guillon98] C. Guillon, M. E. van der Ende, P. H. Boers, R. A. Gruters, M. Schutten, A. D. Osterhaus, Coreceptor usage of human immunodeficiency virus type 2 primary isolates and biological clones is broad and does not correlate with their syncytium-inducing capacities, J Virol,72:6260-3 (1998).

[He97] J. He, Y. Chen, M. Farzan, H. Choe, A. Ohagen, S. Gartner, J. Busciglio, X. Yang, W. Hofmann, W. Newman, C. R. Mackay, J. Sodroski, D. Gabuzda, CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia, Nature,385:645-9 (1997).

[Heredia97] A. Heredia, A. Vallejo, V. Soriano, J. S. Epstein, I. K. Hewlett, Chemokine receptors and HIV-2 [letter], AIDS,11:1198-9 (1997).

[Hill97] C. M. Hill, H. Deng, D. Unutmaz, V. N. Kewalramani, L. Bastiani, M. K. Gorny, S. Zolla-Pazner, D. R. Littman, Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor, J Virol,71:6296-304 (1997).

[Hill98] C. M. Hill, D. Kwon, M. Jones, C. B. Davis, S. Marmon, B. L. Daugherty, J. A. DeMartino, M. S. Springer, D. Unutmaz, D. R. Littman, The amino terminus of human CCR5 is required for its function as a receptor for diverse human and simian immunodeficiency virus envelope glycoproteins, Virology,248:357-71 (1998).

[Hirsch94] V. M. Hirsch, J. E. Martin, G. Dapolito, W. R. Elkins, W. T. London, S. Goldstein, P. R. Johnson, Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus, J Virol,68:2649-61 (1994).

[Hirsch95] V. M. Hirsch, G. Dapolito, P. R. Johnson, W. R. Elkins, W. T. London, R. J. Montali, S. Goldstein, C. Brown, Induction of AIDS by simian immunodeficiency virus from an African green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication, J Virol,69:955-67 (1995).

[Hirsch97] V. Hirsch, D. Adger-Johnson, B. Campbell, S. Goldstein, C. Brown, W. R. Elkins, D. C. Montefiori, A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3, J Virol,71:1608-20 (1997).

[Kirchhoff94] F. Kirchhoff, K. Mori, R. C. Desrosiers, The V3 domain is a determinant of simian immunodeficiency virus cell tropism, J Virol,68:3682-92 (1994).

[Kirchhoff97] F. Kirchhoff, S. Pohlmann, M. Hamacher, R. E. Means, T. Kraus, K. Uberla, P. Di Marzio, Simian immunodeficiency virus variants with differential T-cell and macrophage tropism use CCR5 and an unidentified cofactor expressed in CEMx174 cells for efficient entry, J Virol,71:6509-16 (1997).

[Koenig89] S. Koenig, V. M. Hirsch, R. A. Olmsted, D. Powell, W. Maury, A. Rabson, A. S. Fauci, R. H. Purcell, P. R. Johnson, Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein- induced fusion, Proc Natl Acad Sci U S A,86:2443-7 (1989).

[Kozak97] S. L. Kozak, E. J. Platt, N. Madani, F. E. Ferro Jr, K. Peden, D. Kabat, CD4, CXCR-4, and CCR-5 dependencies for infections by primary patient and laboratory-adapted isolates of human immunodeficiency virus type 1, J Virol,71:873-82 (1997).

[Kuhmann97] S. E. Kuhmann, E. J. Platt, S. L. Kozak, D. Kabat, Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses, J Virol,71:8642-56 (1997).

[Liao97] F. Liao, G. Alkhatib, K. W. Peden, G. Sharma, E. A. Berger, J. M. Farber, STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1, J Exp Med,185:2015-23 (1997).

[Liu96] R. Liu, W. A. Paxton, S. Choe, D. Ceradini, S. R. Martin, R. Horuk, M. E. MacDonald, H. Stuhlmann, R. A. Koup, N. R. Landau, Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection, Cell,86:367-77 (1996).

[Lu97] Z. Lu, J. F. Berson, Y. Chen, J. D. Turner, T. Zhang, M. Sharron, M. H. Jenks, Z. Wang, J. Kim, J. Rucker, J. A. Hoxie, S. C. Peiper, R. W. Doms, Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and CXCR4 domains, Proc Natl Acad Sci U S A,94:6426-31 (1997).

[Luciw92] P. A. Luciw, K. E. Shaw, R. E. Unger, V. Planelles, M. W. Stout, J. E. Lackner, E. Pratt-Lowe, N. J. Leung, B. Banapour, M. L. Marthas, Genetic and biological comparisons of pathogenic and nonpathogenic molecular clones of simian immunodeficiency virus (SIVmac), AIDS Res Hum Retroviruses,8:395-402 (1992).

[Marcon97] L. Marcon, H. Choe, K. A. Martin, M. Farzan, P. D. Ponath, L. Wu, W. Newman, N. Gerard, C. Gerard, J. Sodroski, Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239, J Virol,71:2522-7 (1997).

[Marx98] P. A. Marx, Z. Chen, The function of simian chemokine receptors in the replication of SIV, Semin Immunol,10:215-23 (1998).

[McKnight98] A. McKnight, M. T. Dittmar, J. Moniz-Periera, K. Ariyoshi, J. D. Reeves, S. Hibbitts, D. Whitby, E. Aarons, A. E. Proudfoot, H. Whittle, P. R. Clapham, A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4, J Virol,72:4065-71 (1998).

[Michael97] N. L. Michael, G. Chang, L. G. Louie, J. R. Mascola, D. Dondero, D. L. Birx, H. W. Sheppard, The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression, Nat Med,3:338-40 (1997).

[Moore97] J. P. Moore, Coreceptors: implications for HIV pathogenesis and therapy, Science,276:51-2 (1997).

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