HIV Databases HIV Databases home HIV Databases home
HIV sequence database



Reagents for HIV/SIV Vaccine Studies

Carla Kuiken

T10, MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545

 

Since last year's edition of this section, a few new attenuated SIVs and SHIVs have been added to the collection. We have attempted to include all strains represented in the literature. If there are any that are not included, we would very much appreciate hearing about them; we will make sure they will be added in the next edition of the Compendium. All isolates have a separate color code, so that identifying the structure and composition of the genome of the strains can be done at a glance. Suggestions to make this section more useful are welcome.

In Figures 1-3 we present an overview of the virus strains that are frequently used in these studies and their derivation. A distinction must be made between strains used for vaccination, which obviously must be non-pathogenic, and strains used for challenge, which tend to be pathogenic. Some strains have been used both as vaccine and as challenge strains. Pathogenicity is relative, and depends on the virus, the host species, and the individual host. For example, SIVsm is not pathogenic in its natural host, the sooty mangabey, but can be highly pathogenic to macaques.

SIVmac viruses are used most extensively in these studies. The SIVmac isolates 251 and 32H both have a less pathogenic counterpart, clones 1A11 and C8, respectively. These clones are genetically very similar to the quasispecies they were derived from, but they have one or more attenuating genetic deletions. Another important SIVmac isolate, 239, is a clonal isolate from rhesus monkey #239. SIVmac239 is pathogenic, but a long series of reduced- or non-pathogenic strains with varying number of deletions in the genome has been derived from it. These strains cover a spectrum of pathogenicity, ranging from highly pathogenic to apparently non-infectious (unable to replicate in the host) (Desrosiers et al. 1998). It has recently become apparent that monkeys infected with SIVmac239-D3, in the lower mid range of the pathogenicity spectrum, do develop AIDS after several years (Cohen 1997). Two macrophage-tropic variants have also been derived from SIVmac-239: SIVmac316 and 17E (see Figure 1a).

SIVsm isolates can be highly pathogenic to macaques. Pathogenic challenge stocks in this group are usually bulk (rather than clonal) isolates, passaged in one of several macaques. Genetic clones of this group (such as SIVsmH4) tend to be much less pathogenic. An important and highly pathogenic strain is SIVsmPBj14, which kills a majority of infected macaques at primary infection, within a few weeks; monkeys that survive primary infection usually die of an AIDS-like illness within two years. Other isolates that have been used as challenge stocks are B670 and E660. Derivation of commonly used isolates from this group is shown in Figure 1b.

In recent years the repertoire of non-pathogenic vaccine strains has been extended by the creation of artificially attenuated virus variants. This is usually done either by creating stop codons in non-vital sections, or deleting sections from the genome of a virulent strain. Figure2 shows a schematic representation of attenuated SIV strains. The diagram shows where changes have been made or documented with respect to the wild type.

Figure 3 gives an overview of SHIV strains that are presently in use in the vaccine field, and indicates which section of the genomes are derived from HIV-1 (and which strain of HIV-1), and which from a SIV strain.

Acknowledgments

We gratefully acknowledge the help of Drs. Jim Bradac and Alan Schultz from NIAID for invaluable background information and helpful suggestions.

 


 

 

 

 

 

 

 

 


Figure 3. Schematic representation of common attenuated SIV strains used in vaccine research. Deletions are indicated in white, mutations are shown as black lines. Mutations may include insertion or deletion of a stop codon.
Notes: SIVmac239, a frequently used pathogenic strain, contains a stop codon (TAA) in nef. BK28 is a clone from the SIVmac251 bulk isolate; it is the only sequence available from SIVmac251. SHIV KU1 and KU2 are passages of SHIV-4. SHIV 98.6P and KB9 are passages of SHIV89.6. SF33A is a passage of SF33.

 

References

Anderson, M. G., D. Hauer, D. P. Sharma, S. V. Joag, O. Narayan, M. C. Zink, and J. E. Clements, 1993. Analysis of envelope changes acquired by SIVmac239 during neuroadaption in rhesus macaques. Virology 195,616-26.

Chen, Z., Y. Huang, X. Zhao, E. Skulsky, D. Lin, J. Ip, A. Gettie, and D. Ho, 2000. Enhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques(macaca nemestrina). J Virol 74(14),6501-6510.

Cohen, J., 1997. Weakened SIV vaccine still kills [news]. Science 278,24-5.

Conway, M. D., B. Davison-Fairburn, L. N. Martin, M. S. Insler, and M. Murphey-Corb, 1991. Infection of rhesus monkeys with topical instillation of simian immunodeficiency virus (SIV)B670 into the conjunctival sac. J Med Primatol 20,152-5.

Desrosiers, R. C., J. D. Lifson, J. S. Gibbs, S. C. Czajak, A. Y. Howe, L. O. Arthur, and R. P. Johnson, 1998. Identification of highly attenuated mutants of simian immunodeficiency virus. J Virol 72,1431-7.

Dewhurst, S., J. E. Embretson, D. C. Anderson, J. I. Mullins, and P. N. Fultz, 1990. Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM- PBj14. Nature 345,636-40.

Etemad-Moghadam, B., G. B. Karlsson, M. Halloran, Y. Sun, D. Schenten, M. Fernandes, N. Letvin, and J. Sodroski, 1998. Characterization of Simian_Human Immunodeficiency Virus Envelope Glycoprotein Epitopes Recognized by Neutralizing Antibodies from Infected Monkeys. J. Virol 72(10),8437-8445.

Heeney, J. L., 1996. Primate models for AIDS vaccine development. AIDS 10 Suppl A,S115-22.

Himathongkham, S., N.S. Halpin, J. Li, M.W. Stout, C. J. Miller, and P.A. Luciw, 2000. Simian-Human immunodeficiency virus containing a human immunodeficiency virus type 2 subtype E envelope gene: persistent infection, CD4+ T-cell depletion, and mucosal membrane transmission in macaques. J Virol 74(17),7851-7860.

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

Joag, S. V., Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, 1996. Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. J Virol 70,3189-97.

Johnson, R. P., and R. C. Desrosiers, 1998. Protective immunity induced by live attenuated simian immunodeficiency virus. Curr Opin Immunol 10,436-43.

Karlsson, G. B., M. Halloran, J. Li, I. W. Park, R. Gomila, K. A. Reimann, M. K. Axthelm, S. A. Iliff, N. L. Letvin, and J. Sodroski, 1997. Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol 71,4218-25.

Kestler, H., T. Kodama, D. Ringler, M. Marthas, N. Pedersen, A. Lackner, D. Regier, P. Sehgal, M. Daniel, N. King, and et al., 1990. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science 248,1109-12.

Klinger, J. M., S. Himathongkham, H. Legg, P.A. Luciw, and S. W. Barnett, 1998. Infection of baboons with simian immunodeficiency virus constructed with an HIV-1 Thai subtype E envelope. AIDS 12,849-857.

Kornfeld, H., N. Riedel, G. A. Viglianti, V. Hirsch, and J. I. Mullins, 1987. Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature 326,610-3.

Liu, Z. Q., S. Mukherjee, M. Sahni, C. McCormick-Davis, K. Leung, Z. Li, V. H. Gattone, C. Tian, R. W. Doms, T. L. Hoffman, R. Raghavan, O. Narayan, and E. B. Stephens, 1999. Derivation and Biological Characterization of a Molecular Clone of SHIVKU-2 That Causes AIDS, Neurological Disease, and Renal Disease in Rhesus Macaques. Virology 260,295-307.

HIV/SIV Vaccine Reagents

Luciw, P. A., E. Pratt-Lowe, K. E. Shaw, J. A. Levy, and C. Cheng-Mayer, 1995. Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV). Proc Natl Acad Sci U S A 92,7490-4.

Marthas, M. L., S. Sutjipto, J. Higgins, B. Lohman, J. Torten, P. A. Luciw, P. A. Marx, and N. C. Pedersen, 1990. Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. J Virol 64,3694-700.

Mori, K., D. J. Ringler, T. Kodama, and R. C. Desrosiers, 1992. Complex determinants of macrophage tropism in env of simian immunodeficiency virus. J Virol 66,2067-75.

Narayan, S. V., S. Mukherjee, F. Jia, Z. Li, C. Wang, L. Foresman, C. McCormick-Davis, E. B. Stephens, S. V. Joag, and O. Narayan, 1999. Characterization of a Neutralization-Escape Variant of SHIVKU-1, a Virus That Causes Acquired Immune Deficiency Syndrome in Pig-Tailed Macaques. Virology 256,54-63.

Novembre, F. J., P. R. Johnson, M. G. Lewis, D. C. Anderson, S. Klumpp, H. M. McClure, and V. M. Hirsch, 1993. Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant. J Virol 67,2466-74.

Novembre, F. J., M. G. Lewis, M. M. Saucier, J. Yalley-Ogunro, T. Brennan, K. McKinnon, S. Bellah, and H. M. McClure, 1996. Deletion of the nef gene abrogates the ability of SIV smmPBj to induce acutely lethal disease in pigtail macaques. AIDS Res Hum Retroviruses 12,727-36.

Raghavan, R., E. B. Stephens, S. V. Joag, I. Adany, D. M. Pinson, Z. Li, F. Jia, M. Sahni, C. Wang, K. Leung, L. Foresman, and O. Narayan, 1997. Neuropathogenesis of chimeric simian/human immunodeficiency virus infection in pig-tailed and rhesus macaques. Brain Pathol 7,851-61.

Reimann, K. A., J. T. Li, R. Veazey, M. Halloran, I. W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin, 1996. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS- like disease after in vivo passage in rhesus monkeys. J Virol 70,6922-8.

Reimann, K. A., J. T. Li, G. Voss, C. Lekutis, K. Tenner-Racz, P. Racz, W. Lin, D. C. Montefiori, D. E. Lee-Parritz, Y. Lu, R. G. Collman, J. Sodroski, and N. L. Letvin, 1996. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. J Virol 70,3198-206.

Rud, E. W., J. R. Yon, B. A. Larder, B. E. Clarke, N. Cook, and M. Cranage. 1992. Infectious molecular clones of SIVmac32: Nef deletion controls ability to reisolate virus from rhesus macaques, p. 229-235. In F.Brown and R.M.Chanock and H.S.Ginsberg and R.A.Lerner (ed.), Vaccines. Cold Spring Harbor Laboratory Press, New York.

Ruprecht, R. M., T. W. Baba, V. Liska, R. Bronson, D. Penninck, and M. F. Greene, 1996. "Attenuated" simian immunodeficiency virus in macaque neonates. AIDS Res Hum Retroviruses 12,45960.

Schultz, A. M., and S. L. Hu, 1993. Primate models for HIV vaccines. AIDS 7 Suppl 1,S161-70.

Shibata, R., F. Maldarelli, C. Siemon, T. Matano, M. Parta, G. Miller, T. Fredrickson, and M. A. Martin, 1997. Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing. J Infect Dis 176,362-73.

Shibata, R., T. Igarashi, N. Haigwood, A. Buckler-White, R. Ogert, W. Ross, R. Willey, M. W. Cho, and M. A. Martin, 1999. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nat. Med. 5(2),204-210.

Shinohara, K., K. Sakai, S. Ando, Y. Ami, N. Yoshino, E. Takahasi, K. Someya, Y. Suzaki, T. Nakasone, Y. Sasaki, M. Kaizu, Y. Lu, and M. Honda, 1999. A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey. J. Gen. Virol. 80, 1231-1240.

Villinger, F., S. S. Brar, G. T. Brice, N. F. Chikkala, F. J. Novembre, A. E. Mayne, S. Bucur, C. D. Hillyer, and A. A. Ansari, 1997. Immune and hematopoietic parameters in HIV-1-infected chimpanzees during clinical progression toward AIDS. J Med Primatol 26,11-8.

last modified: Wed May 1 13:06 2013


Questions or comments? Contact us at seq-info@lanl.gov.

 
Operated by Los Alamos National Security, LLC, for the U.S. Department of Energy's National Nuclear Security Administration
Copyright © 2005-2012 LANS LLC All rights reserved | Disclaimer/Privacy

Dept of Health & Human Services Los Alamos National Institutes of Health