This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.00202-07v1 81/11/5594    most recent 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 Brown, C. R. Articles by Hirsch, V. M. Search for Related Content PubMed PubMed Citation Articles by Brown, C. R. Articles by Hirsch, V. M.

 Previous Article  |  Next Article 

Journal of Virology, June 2007, p. 5594-5606, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00202-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Unique Pathology in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques Is Consistent with a Pathogenesis Distinct from That of Classical AIDS

Laboratory of Molecular Microbiology,¹ Research Technology Branch, NIAID, NIH, 4 Center Drive, Bethesda, Maryland 20892²

Received 29 January 2007/ Accepted 14 March 2007

Simian immunodeficiency virus (SIV) infection of macaques and human immunodeficiency virus type 1 (HIV-1) infection of humans result in variable but generally fatal disease outcomes. Most SIV-infected macaques progress to AIDS over a period of 1 to 3 years, in the face of robust SIV-specific immune responses (conventional progressors [CP]). A small number of SIV-inoculated macaques mount transient immune responses and progress rapidly to AIDS (rapid progressors [RP]). We speculated that the underlying pathogenic mechanisms may differ between RP and CP macaques. We compared the pathological lesions, virus loads, and distribution of virus and target cells in SIVsmE660- or SIVsmE543-infected RP and CP rhesus macaques at terminal disease. RP macaques developed a wasting syndrome characterized by severe SIV enteropathy in the absence of opportunistic infections. In contrast, opportunistic infections were commonly observed in CP macaques. RP and CP macaques showed distinct patterns of CD4⁺ T-cell depletion, with a selective loss of memory cells in RP macaques and a generalized (naive and memory) CD4 depletion in CP macaques. In situ hybridization demonstrated higher levels of virus expression in lymphoid tissues (P < 0.001) of RP macaques and a broader distribution to include many nonlymphoid tissues. Finally, SIV was preferentially expressed in macrophages in RP macaques whereas the primary target cells in CP macaques were T lymphocytes at end stage disease. These data suggest distinct pathogenic mechanisms leading to the deaths of these two groups of animals, with CP macaques being more representative of HIV-induced AIDS in humans.

Published ahead of print on 21 March 2007.

This article has been cited by other articles:

• Veazey, R. S., Acierno, P. M., McEvers, K. J., Baumeister, S. H. C., Foster, G. J., Rett, M. D., Newberg, M. H., Kuroda, M. J., Williams, K., Kim, E.-Y., Wolinsky, S. M., Rieber, E. P., Piatak, M. Jr., Lifson, J. D., Montefiori, D. C., Brown, C. R., Hirsch, V. M., Schmitz, J. E. (2008). Increased Loss of CCR5+ CD45RA- CD4+ T Cells in CD8+ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys. J. Virol. 82: 5618-5630 [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]