1887

Journal of General Virology header logo

Volume 91, Issue 3

Small intestine CD4 cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load Free

Abstract

Human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (SHIV) infection generally lead to death of the host accompanied by high viraemia and profound CD4 T-cell depletion. SHIV clone KS661-infected rhesus macaques with a high viral load set point (HVL) ultimately experience diarrhoea and wasting at 6–12 months after infection. In contrast, infected macaques with a low viral load set point (LVL) usually live asymptomatically throughout the observation period, and are therefore referred to as asymptomatic LVL (Asym LVL) macaques. Interestingly, some LVL macaques exhibit diarrhoea and wasting similar to the symptoms of HVL macaques and are termed symptomatic LVL (Sym LVL) macaques. This study tested the hypothesis that Sym LVL macaques have the same degree of intestinal abnormalities as HVL macaques. The proviral DNA loads in lymphoid tissue and the intestines of Sym LVL and Asym LVL macaques were comparable and all infected monkeys showed villous atrophy. Notably, the CD4 cell frequencies of lymphoid tissues and intestines in Sym LVL macaques were remarkably lower than those in Asym LVL and uninfected macaques. Furthermore, Sym LVL and HVL macaques exhibited an increased number of activated macrophages. In conclusion, intestinal disorders including CD4 cell reduction and abnormal immune activation can be observed in SHIV-KS661-infected macaques independent of virus replication levels.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.017368-0
2010-03-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/3/773.html?itemId=/content/journal/jgv/10.1099/vir.0.017368-0&mimeType=html&fmt=ahah

References

  1. Anton P. A., Elliott J., Poles M. A., McGowan I. M., Matud J., Hultin L. E., Grovit-Ferbas K., Mackay C. R., Chen I. S. Y., Giorgi J. V. 2000; Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue. AIDS 14:1761–1765 [CrossRef]
     [Google Scholar]
  2. Batman P. A., Miller A. R., Forster S. M., Harris J. R., Pinching A. J., Griffin G. E. 1989; Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. J Clin Pathol 42:275–281 [CrossRef]
     [Google Scholar]
  3. Brenchley J. M., Schacker T. W., Ruff L. E., Price D. A., Taylor J. H., Beilman G. J., Nguyen P. L., Khoruts A., Larson M. et al. 2004; CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200:749–759 [CrossRef]
     [Google Scholar]
  4. Brenchley J. M., Price D. A., Schacker T. W., Asher T. E., Silvestri G., Rao S., Kazzaz Z., Bornstein E., Lambotte O. et al. 2006; Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12:1365–1371
     [Google Scholar]
  5. Fackler O. T., Schafer M., Schmidt W., Zippel T., Heise W., Schneider T., Zeitz M., Riecken E. O., Mueller-Lantzsch N., Ullrich R. 1998; HIV-1 p24 but not proviral load is increased in the intestinal mucosa compared with the peripheral blood in HIV-infected patients. AIDS 12:139–146 [CrossRef]
     [Google Scholar]
  6. Fukazawa Y., Miyake A., Ibuki K., Inaba K., Saito N., Motohara M., Horiuchi R., Himeno A., Matsuda K. et al. 2008; Small intestine CD4+ T cells are profoundly depleted during acute simian–human immunodeficiency virus infection, regardless of viral pathogenicity. J Virol 82:6039–6044 [CrossRef]
     [Google Scholar]
  7. Gibbons T., Fuchs G. J. 2007; Chronic enteropathy: clinical aspects. Nestle Nutr Workshop Ser Pediatr Program 59:89–101
     [Google Scholar]
  8. Hazenberg M. D., Otto S. A., van Benthem B. H., Roos M. T., Coutinho R. A., Lange J. M., Hamann D., Prins M., Miedema F. 2003; Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS 17:1881–1888 [CrossRef]
     [Google Scholar]
  9. Hunt P. W., Brenchley J., Sinclair E., McCune J. M., Roland M., Page-Shafer K., Hsue P., Emu B., Krone M. et al. 2008; Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis 197:126–133 [CrossRef]
     [Google Scholar]
  10. Isbel N. M., Nikolic-Paterson D. J., Hill P. A., Dowling J., Atkins R. C. 2001; Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis. Nephrol Dial Transplant 16:1638–1647 [CrossRef]
     [Google Scholar]
  11. Kahn E. 1997; Gastrointestinal manifestations in pediatric AIDS. Pediatr Pathol Lab Med 17:171–208
     [Google Scholar]
  12. Kaufmann G. R., Perrin L., Pantaleo G., Opravil M., Furrer H., Telenti A., Hirschel B., Ledergerber B., Vernazza P. et al. 2003; CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 163:2187–2195 [CrossRef]
     [Google Scholar]
  13. Kotler D. P. 2005; HIV infection and the gastrointestinal tract. AIDS 19:107–117 [CrossRef]
     [Google Scholar]
  14. Lapenta C., Boirivant M., Marini M., Santini S. M., Logozzi M., Viora M., Belardelli F., Fais S. 1999; Human intestinal lamina propria lymphocytes are naturally permissive to HIV-1 infection. Eur J Immunol 29:1202–1208 [CrossRef]
     [Google Scholar]
  15. Ling B., Veazey R. S., Hart M., Lackner A. A., Kuroda M., Pahar B., Marx P. A. 2007; Early restoration of mucosal CD4 memory CCR5 T cells in the gut of SIV-infected rhesus predicts long term non-progression. AIDS 21:2377–2385 [CrossRef]
     [Google Scholar]
  16. Madec Y., Boufassa F., Porter K., Meyer L. 2005; Spontaneous control of viral load and CD4 cell count progression among HIV-1 seroconverters. AIDS 19:2001–2007 [CrossRef]
     [Google Scholar]
  17. Maloy K. J., Salaun L., Cahill R., Dougan G., Saunders N. J., Powrie F. 2003; CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197:111–119
     [Google Scholar]
  18. Marchetti G., Gori A., Casabianca A., Magnani M., Franzetti F., Clerici M., Perno C. F., Monforte A., Galli M., Meroni L. 2006; Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART. AIDS 20:1727–1736 [CrossRef]
     [Google Scholar]
  19. Marchetti G., Bellistri G. M., Borghi E., Tincati C., Ferramosca S., La Francesca M., Morace G., Gori A., Monforte A. D. 2008; Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS 22:2035–2038 [CrossRef]
     [Google Scholar]
  20. Miyake A., Ibuki K., Enose Y., Suzuki H., Horiuchi R., Motohara M., Saito N., Nakasone T., Honda M. et al. 2006; Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection. J Gen Virol 87:1311–1320 [CrossRef]
     [Google Scholar]
  21. Montefiori D. C., Reimann K. A., Wyand M. S., Manson K., Lewis M. G., Collman R. G., Sodroski J. G., Bolognesi D. P., Letvin N. L. 1998; Neutralizing antibodies in sera from macaques infected with chimeric simian–human immunodeficiency virus containing the envelope glycoproteins of either a laboratory-adapted variant or a primary isolate of human immunodeficiency virus type 1. J Virol 72:3427–3431
     [Google Scholar]
  22. Motohara M., Ibuki K., Miyake A., Fukazawa Y., Inaba K., Suzuki H., Masuda K., Minato N., Kawamoto H. et al. 2006; Impaired T-cell differentiation in the thymus at the early stages of acute pathogenic chimeric simian–human immunodeficiency virus (SHIV) infection in contrast to less pathogenic SHIV infection. Microbes Infect 8:1539–1549 [CrossRef]
     [Google Scholar]
  23. Norton W. T. 1999; Cell reactions following acute brain injury: a review. Neurochem Res 24:213–218 [CrossRef]
     [Google Scholar]
  24. Paiardini M., Frank I., Pandrea I., Apetrei C., Silvestri G. 2008; Mucosal immune dysfunction in AIDS pathogenesis. AIDS Rev 10:36–46
     [Google Scholar]
  25. Piketty C., Castiel P., Belec L., Batisse D., Si Mohamed A., Gilquin J., Gonzalez-Canali G., Jayle D., Karmochkine M. et al. 1998; Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS 12:745–750 [CrossRef]
     [Google Scholar]
  26. Sestak K. 2005; Chronic diarrhea and AIDS: insights into studies with non-human primates. Curr HIV Res 3:199–205 [CrossRef]
     [Google Scholar]
  27. Sharpstone D., Gazzard B. 1996; Gastrointestinal manifestations of HIV infection. Lancet 348:379–383 [CrossRef]
     [Google Scholar]
  28. Shinohara K., Sakai K., Ando S., Ami Y., Yoshino N., Takahashi E., Someya K., Suzaki Y., Nakasone T. et al. 1999; A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey. J Gen Virol 80:1231–1240
     [Google Scholar]
  29. Smith P. D., Meng G., Salazar-Gonzalez J. F., Shaw G. M. 2003; Macrophage HIV-1 infection and the gastrointestinal tract reservoir. J Leukoc Biol 74:642–649 [CrossRef]
     [Google Scholar]
  30. Veazey R. S., DeMaria M., Chalifoux L. V., Shvetz D. E., Pauley D. R., Knight H. L., Rosenzweig M., Johnson R. P., Desrosiers R. C., Lackner A. A. 1998; Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427–431 [CrossRef]
     [Google Scholar]
  31. Veazey R. S., Mansfield K. G., Tham I. C., Carville A. C., Shvetz D. E., Forand A. E., Lackner A. A. 2000a; Dynamics of CCR5 expression by CD4+ T cells in lymphoid tissues during simian immunodeficiency virus infection. J Virol 74:11001–11007 [CrossRef]
     [Google Scholar]
  32. Veazey R. S., Tham I. C., Mansfield K. G., DeMaria M., Forand A. E., Shvetz D. E., Chalifoux L. V., Sehgal P. K., Lackner A. A. 2000b; Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4+ T cells are rapidly eliminated in early SIV infection in vivo. J Virol 74:57–64 [CrossRef]
     [Google Scholar]
  33. Wilcox C. M., Saag M. S. 2008; Gastrointestinal complications of HIV infection: changing priorities in the HAART era. Gut 57:861–870 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.017368-0
Loading
Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load
J. Gen. Virol. 91, 773 (2010); https://doi.org/10.1099/vir.0.017368-0
/content/journal/jgv/10.1099/vir.0.017368-0
/content/journal/jgv/10.1099/vir.0.017368-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error