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

Charles R. Brown,1 Meggan Czapiga,2 Juraj Kabat,2 Que Dang,1 Ilnour Ourmanov,1 Yoshiaki Nishimura,1 Malcolm A. Martin,1 and Vanessa M. Hirsch1*

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.

* Corresponding author. Mailing address: LMM, NIAID, NIH, Building 4, Room B1-41, 4 Center Drive, Bethesda, MD 20892. Phone: (301) 496-0559. Fax: (301) 480-3129. E-mail: vhirsch{at}niaid.nih.gov

{triangledown} Published ahead of print on 21 March 2007.

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.



This article has been cited by other articles:

  • Ryzhova, E., Aye, P., Harvey, T., Cao, W., Lackner, A., Gonzalez-Scarano, F. (2009). Intrathecal Humoral Responses Are Inversely Associated with the Frequency of Simian Immunodeficiency Virus Macrophage-Tropic Variants in the Central Nervous System. J. Virol. 83: 8282-8288 [Abstract] [Full Text]  
  • Wilson, N. A., Keele, B. F., Reed, J. S., Piaskowski, S. M., MacNair, C. E., Bett, A. J., Liang, X., Wang, F., Thoryk, E., Heidecker, G. J., Citron, M. P., Huang, L., Lin, J., Vitelli, S., Ahn, C. D., Kaizu, M., Maness, N. J., Reynolds, M. R., Friedrich, T. C., Loffredo, J. T., Rakasz, E. G., Erickson, S., Allison, D. B., Piatak, M. Jr., Lifson, J. D., Shiver, J. W., Casimiro, D. R., Shaw, G. M., Hahn, B. H., Watkins, D. I. (2009). Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge. J. Virol. 83: 6508-6521 [Abstract] [Full Text]  
  • Yeh, W. W., Jaru-ampornpan, P., Nevidomskyte, D., Asmal, M., Rao, S. S., Buzby, A. P., Montefiori, D. C., Korber, B. T., Letvin, N. L. (2009). Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate. J. Virol. 83: 2686-2696 [Abstract] [Full Text]  
  • Souquiere, S., Onanga, R., Makuwa, M., Pandrea, I., Ngari, P., Rouquet, P., Bourry, O., Kazanji, M., Apetrei, C., Simon, F., Roques, P. (2009). Simian immunodeficiency virus types 1 and 2 (SIV mnd 1 and 2) have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission. J. Gen. Virol. 90: 488-499 [Abstract] [Full Text]  
  • Reynolds, M. R., Weiler, A. M., Weisgrau, K. L., Piaskowski, S. M., Furlott, J. R., Weinfurter, J. T., Kaizu, M., Soma, T., Leon, E. J., MacNair, C., Leaman, D. P., Zwick, M. B., Gostick, E., Musani, S. K., Price, D. A., Friedrich, T. C., Rakasz, E. G., Wilson, N. A., McDermott, A. B., Boyle, R., Allison, D. B., Burton, D. R., Koff, W. C., Watkins, D. I. (2008). Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. JEM 205: 2537-2550 [Abstract] [Full Text]  
  • 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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»