This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuwata, T. Articles by Hirsch, V. M. Search for Related Content PubMed PubMed Citation Articles by Kuwata, T. Articles by Hirsch, V. M.

 Previous Article  |  Next Article 

Journal of Virology, February 2006, p. 1463-1475, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1463-1475.2006

Infectious Molecular Clones from a Simian Immunodeficiency Virus-Infected Rapid-Progressor (RP) Macaque: Evidence of Differential Selection of RP-Specific Envelope Mutations In Vitro and In Vivo

Takeo Kuwata,¹ Houman Dehghani,^1, Charles R. Brown,¹ Ronald Plishka,¹ Alicia Buckler-White,¹ Tatsuhiko Igarashi,¹ Joseph Mattapallil,² Mario Roederer,² and Vanessa M. Hirsch^1*

Laboratory of Molecular Microbiology,¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892²

Received 19 September 2005/ Accepted 4 November 2005

A minor fraction of simian immunodeficiency virus (SIV)-infected macaques progress rapidly to AIDS in the absence of SIV-specific immune responses. Common mutations in conserved residues of env in three SIVsmE543-3-infected rapid-progressor (RP) macaques suggest the evolution of a common viral variant in RP macaques. The goal of the present study was to analyze the biological properties of these variants in vitro and in vivo through the derivation of infectious molecular clones. Virus isolated from a SIVsmE543-3-infected RP macaque, H445 was used to inoculate six naive rhesus macaques. Although RP-specific mutations dominated in H445 tissues, they represented only 10% of the population of the virus stock, suggesting a selective disadvantage in vitro. Only one of these macaques (H635) progressed rapidly to AIDS. Plasma virus during primary infection of H635 was similar to the inoculum. However, RP-specific mutations were apparently rapidly reselected by 4 to 9 weeks postinfection. Terminal plasma from H635 was used as a source of viral RNA to generate seven full-length, infectious molecular clones. With the exception of one clone, which was similar to SIVsmE543-3, clones with RP-specific mutations replicated with delayed kinetics in rhesus peripheral blood mononuclear cells and human T-cell lines. None of the clones replicated in monocyte-derived or alveolar macrophages, and all used CCR5 as their major coreceptor. RP variants appear to be well adapted to replicate in vivo in RP macaques but are at a disadvantage in tissue culture compared to their parent, SIVsmE543-3. Therefore, tissue culture may not provide a good surrogate for replication of RP variants in macaques. These infectious clones will provide a valuable reagent to study the roles of specific viral variants in rapid progression in vivo.

Present address: Amgen, 51 University St., Seattle, WA 98101.

This article has been cited by other articles:

• Peut, V., Kent, S. J. (2007). Utility of Human Immunodeficiency Virus Type 1 Envelope as a T-Cell Immunogen. J. Virol. 81: 13125-13134 [Abstract] [Full Text]  
• Kuwata, T., Byrum, R., Whitted, S., Goeken, R., Buckler-White, A., Plishka, R., Iyengar, R., Hirsch, V. M. (2007). A Rapid Progressor-Specific Variant Clone of Simian Immunodeficiency Virus Replicates Efficiently In Vivo Only in the Absence of Immune Reponses. J. Virol. 81: 8891-8904 [Abstract] [Full Text]  
• Brown, C. R., Czapiga, M., Kabat, J., Dang, Q., Ourmanov, I., Nishimura, Y., Martin, M. A., Hirsch, V. M. (2007). Unique Pathology in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques Is Consistent with a Pathogenesis Distinct from That of Classical AIDS. J. Virol. 81: 5594-5606 [Abstract] [Full Text]