1887

Abstract

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4 T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2014-01-01
2024-12-03
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References

  1. Ali A., Rudge P., Dalgleish A. G. 1992; Neopterin concentrations in serum and cerebrospinal fluid in HTLV-I infected individuals. J Neurol 239:270–272[PubMed]
    [Google Scholar]
  2. Apetrei C., Sumpter B., Souquiere S., Chahroudi A., Makuwa M., Reed P., Ribeiro R. M., Pandrea I., Roques P., Silvestri G. 2011; Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills (Mandrillus sphinx). J Virol 85:13077–13087 [View Article][PubMed]
    [Google Scholar]
  3. Beaumier C. M., Harris L. D., Goldstein S., Klatt N. R., Whitted S., McGinty J., Apetrei C., Pandrea I., Hirsch V. M., Brenchley J. M. 2009; CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat Med 15:879–885 [View Article][PubMed]
    [Google Scholar]
  4. Bosinger S. E., Li Q., Gordon S. N., Klatt N. R., Duan L., Xu L., Francella N., Sidahmed A., Smith A. J. other authors 2009; Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119:3556–3572[PubMed]
    [Google Scholar]
  5. Chahroudi A., Bosinger S. E., Vanderford T. H., Paiardini M., Silvestri G. 2012; Natural SIV hosts: showing AIDS the door. Science 335:1188–1193 [View Article][PubMed]
    [Google Scholar]
  6. Fouchet D., Verrier D., Ngoubangoye B., Souquière S., Makuwa M., Kazanji M., Gonzalez J. P., Pontier D. 2012; Natural simian immunodeficiency virus transmission in mandrills: a family affair?. Proc Biol Sci 279:3426–3435 [View Article][PubMed]
    [Google Scholar]
  7. Fuchs D., Spira T. J., Hausen A., Reibnegger G., Werner E. R., Felmayer G. W., Wachter H. 1989; Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection. Clin Chem 35:1746–1749[PubMed]
    [Google Scholar]
  8. Gifford R. J., Katzourakis A., Tristem M., Pybus O. G., Winters M., Shafer R. W. 2008; A transitional endogenous lentivirus from the genome of a basal primate and implications for lentivirus evolution. Proc Natl Acad Sci U S A 105:20362–20367 [View Article][PubMed]
    [Google Scholar]
  9. Gilden R. V., Arthur L. O., Robey W. G., Kelliher J. C., Graham C. E., Fischinger P. J. 1986; HTLV-III antibody in a breeding chimpanzee not experimentally exposed to the virus. Lancet 327:678–679 [View Article][PubMed]
    [Google Scholar]
  10. Gordon S. N., Klatt N. R., Bosinger S. E., Brenchley J. M., Milush J. M., Engram J. C., Dunham R. M., Paiardini M., Klucking S. other authors 2007; Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 179:3026–3034[PubMed] [CrossRef]
    [Google Scholar]
  11. Kaur A., Hale C. L., Ramanujan S., Jain R. K., Johnson R. P. 2000; Differential dynamics of CD4+ and CD8+ T-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection. J Virol 74:8413–8424 [View Article][PubMed]
    [Google Scholar]
  12. Keele B. F., Jones J. H., Terio K. A., Estes J. D., Rudicell R. S., Wilson M. L., Li Y., Learn G. H., Beasley T. M. other authors 2009; Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 460:515–519 [View Article][PubMed]
    [Google Scholar]
  13. Kornfeld C., Ploquin M. J., Pandrea I., Faye A., Onanga R., Apetrei C., Poaty-Mavoungou V., Rouquet P., Estaquier J. other authors 2005; Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 115:1082–1091[PubMed] [CrossRef]
    [Google Scholar]
  14. Lambin P., Desjobert H., Debbia M., Fine J. M., Muller J. Y. 1986; Serum neopterin and beta 2-microglobulin in anti-HIV positive blood donors. Lancet 328:1216 [View Article][PubMed]
    [Google Scholar]
  15. Liégeois F., Verrier D., Greenwood E., Schmidt F., Heeney J., Rouet F. 2012; Control of simian immunodeficiency virus SIVmnd-1 RNA plasma viremia after coinfection or superinfection with SIVmnd-1 in SIVmnd-2-infected mandrills and vice versa. J Virol 86:2385–2386 author reply 2387–2388 [View Article][PubMed]
    [Google Scholar]
  16. Ma D., Jasinska A., Kristoff J., Grobler J. P., Turner T., Jung Y., Schmitt C., Raehtz K., Feyertag F. other authors 2013; SIVagm infection in wild African green monkeys from South Africa: epidemiology, natural history, and evolutionary considerations. PLoS Pathog 9:e1003011 [View Article][PubMed]
    [Google Scholar]
  17. Milush J. M., Mir K. D., Sundaravaradan V., Gordon S. N., Engram J., Cano C. A., Reeves J. D., Anton E., O’Neill E. other authors 2011; Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells. J Clin Invest 121:1102–1110 [View Article][PubMed]
    [Google Scholar]
  18. Moir S., Ho J., Malaspina A., Wang W., DiPoto A. C., O’Shea M. A., Roby G., Kottilil S., Arthos J. other authors 2008; Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 205:1797–1805 [View Article][PubMed]
    [Google Scholar]
  19. Murayama Y., Mukai R., Inoue-Murayama M., Yoshikawa Y. 1999; An African green monkey lacking peripheral CD4 lymphocytes that retains helper T cell activity and coexists with SIVagm. Clin Exp Immunol 117:504–512 [View Article][PubMed]
    [Google Scholar]
  20. Onanga R., Kornfeld C., Pandrea I., Estaquier J., Souquière S., Rouquet P., Mavoungou V. P., Bourry O., M’Boup S. other authors 2002; High levels of viral replication contrast with only transient changes in CD4+ and CD8+ cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx . J Virol 76:10256–10263 [View Article][PubMed]
    [Google Scholar]
  21. Paiardini M., Cervasi B., Reyes-Aviles E., Micci L., Ortiz A. M., Chahroudi A., Vinton C., Gordon S. N., Bosinger S. E. other authors 2011; Low levels of SIV infection in sooty mangabey central memory CD4+ T cells are associated with limited CCR5 expression. Nat Med 17:830–836 [View Article][PubMed]
    [Google Scholar]
  22. Pandrea I., Onanga R., Rouquet P., Bourry O., Ngari P., Wickings E. J., Roques P., Apetrei C. 2001; Chronic SIV infection ultimately causes immunodeficiency in African non-human primates. AIDS 15:2461–2462 [View Article][PubMed]
    [Google Scholar]
  23. Pandrea I., Onanga R., Kornfeld C., Rouquet P., Bourry O., Clifford S., Telfer P. T., Abernethy K., White L. T. other authors 2003; High levels of SIVmnd-1 replication in chronically infected Mandrillus sphinx . Virology 317:119–127 [View Article][PubMed]
    [Google Scholar]
  24. Pandrea I., Apetrei C., Gordon S., Barbercheck J., Dufour J., Bohm R., Sumpter B., Roques P., Marx P. A. other authors 2007a; Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts. Blood 109:1069–1076 [View Article][PubMed]
    [Google Scholar]
  25. Pandrea I. V., Gautam R., Ribeiro R. M., Brenchley J. M., Butler I. F., Pattison M., Rasmussen T., Marx P. A., Silvestri G. other authors 2007b; Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol 179:3035–3046[PubMed] [CrossRef]
    [Google Scholar]
  26. Pandrea I., Onanga R., Souquiere S., Mouinga-Ondéme A., Bourry O., Makuwa M., Rouquet P., Silvestri G., Simon F. other authors 2008; Paucity of CD4+ CCR5+ T cells may prevent transmission of simian immunodeficiency virus in natural nonhuman primate hosts by breast-feeding. J Virol 82:5501–5509 [View Article][PubMed]
    [Google Scholar]
  27. Pandrea I., Silvestri G., Apetrei C. 2009; AIDS in African nonhuman primate hosts of SIVs: a new paradigm of SIV infection. Curr HIV Res 7:57–72 [View Article][PubMed]
    [Google Scholar]
  28. Sachsenberg N., Perelson A. S., Yerly S., Schockmel G. A., Leduc D., Hirschel B., Perrin L. 1998; Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 187:1295–1303 [View Article][PubMed]
    [Google Scholar]
  29. Schacker T. W., Nguyen P. L., Beilman G. J., Wolinsky S., Larson M., Reilly C., Haase A. T. 2002; Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis. J Clin Invest 110:1133–1139[PubMed] [CrossRef]
    [Google Scholar]
  30. Setchell J., Charpentier M., Wickings E. J. 2005; Sexual selection and reproductive careers in mandrills (Mandrillus sphinx). Behav Ecol Sociobiol 58:474–485 [View Article]
    [Google Scholar]
  31. Silvestri G., Sodora D. L., Koup R. A., Paiardini M., O’Neil S. P., McClure H. M., Staprans S. I., Feinberg M. B. 2003; Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18:441–452 [View Article][PubMed]
    [Google Scholar]
  32. Simon F., Souquière S., Damond F., Kfutwah A., Makuwa M., Leroy E., Rouquet P., Berthier J. L., Rigoulet J. other authors 2001; Synthetic peptide strategy for the detection of and discrimination among highly divergent primate lentiviruses. AIDS Res Hum Retroviruses 17:937–952 [View Article][PubMed]
    [Google Scholar]
  33. Souquière S., Mouinga-Ondemé A., Makuwa M., Hermine O., Kazanji M. 2009; Dynamic interaction between STLV-1 proviral load and T-cell response during chronic infection and after immunosuppression in non-human primates. PLoS ONE 4:e6050 [View Article][PubMed]
    [Google Scholar]
  34. Sumpter B., Dunham R., Gordon S., Engram J., Hennessy M., Kinter A., Paiardini M., Cervasi B., Klatt N. other authors 2007; Correlates of preserved CD4+ T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis. J Immunol 178:1680–1691[PubMed] [CrossRef]
    [Google Scholar]
  35. Taaffe J., Chahroudi A., Engram J., Sumpter B., Meeker T., Ratcliffe S., Paiardini M., Else J., Silvestri G. 2010; A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4+ T-cell count whose magnitude is not predicted by viral load or immune activation. J Virol 84:5476–5484 [View Article][PubMed]
    [Google Scholar]
  36. Titanji K., Velu V., Chennareddi L., Vijay-Kumar M., Gewirtz A. T., Freeman G. J., Amara R. R. 2010; Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques. J Clin Invest 120:3878–3890 [View Article][PubMed]
    [Google Scholar]
  37. Traina-Dorge V. L., Lorino R., Gormus B. J., Metzger M., Telfer P., Richardson D., Robertson D. L., Marx P. A., Apetrei C. 2005; Molecular epidemiology of simian T-cell lymphotropic virus type 1 in wild and captive sooty mangabeys. J Virol 79:2541–2548 [View Article][PubMed]
    [Google Scholar]
  38. Triplett T. A., Curti B. D., Bonafede P. R., Miller W. L., Walker E. B., Weinberg A. D. 2012; Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG. Eur J Immunol 42:1893–1905 [View Article][PubMed]
    [Google Scholar]
  39. Veazey R., Ling B., Pandrea I., McClure H., Lackner A., Marx P. 2003; Decreased CCR5 expression on CD4+ T cells of SIV-infected sooty mangabeys. AIDS Res Hum Retroviruses 19:227–233 [View Article][PubMed]
    [Google Scholar]
  40. Vinton C., Klatt N. R., Harris L. D., Briant J. A., Sanders-Beer B. E., Herbert R., Woodward R., Silvestri G., Pandrea I. other authors 2011; CD4-like immunological function by CD4 T cells in multiple natural hosts of simian immunodeficiency virus. J Virol 85:8702–8708 [View Article][PubMed]
    [Google Scholar]
  41. Weiss R. A., Heeney J. L. 2009; Infectious diseases: an ill wind for wild chimps?. Nature 460:470–471 [View Article][PubMed]
    [Google Scholar]
  42. Wickings E. J. 1995; Genetic self-management in a captive colony of mandrills (Mandrillus sphinx) as revealed by DNA minisatellite fingerprints. Electrophoresis 16:1678–1683 [View Article][PubMed]
    [Google Scholar]
  43. Wickings E. J., Dixson A. F. 1992; Development from birth to sexual maturity in a semi-free-ranging colony of mandrills (Mandrillus sphinx) in Gabon. J Reprod Fertil 95:129–138 [View Article][PubMed]
    [Google Scholar]
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