Editors' ChoiceImmunodeficiency viruses

How Some Monkeys Tolerate SIV

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Science Translational Medicine  02 Dec 2009:
Vol. 1, Issue 9, pp. 9ec31
DOI: 10.1126/scitranslmed.3000668

In HIV-infected patients and rhesus monkeys infected with the closely related monkey virus, SIV, the slow decline in the number of circulating immune cells (CD4+ T cells) eventually leads to the severe immunodeficiency of AIDS. But two natural hosts of SIV—the sooty mangabey and the African green monkey—can be infected with SIV and suffer few apparent consequences. Although these monkeys carry a high plasma load of virus, they display few signs of an activated immune system. Under these same circumstances, the SIV-susceptible rhesus monkeys show the pronounced immune activation that eventually promotes T cell exhaustion, depletion, and disease. An understanding of how some monkeys tolerate SIV will likely reveal fundamental facts about HIV and AIDS, but we don’t even know if the natural hosts respond immunologically to SIV at all or whether they dampen the immune response after it occurs. To this end, Bosinger et al. and Jacuelin et al. have used microarrays to track gene expression in blood and lymph node CD4+ T cells in SIV-infected susceptible and resistant monkeys. All three species reacted to infection with a pronounced innate immune response and stimulation of interferon-regulated genes. Although this immune activation persisted in rhesus macaques, it was quickly controlled in the natural hosts, the sooty mangabeys and the African green monkeys. This rapid return to immune homeostasis suggests that the natural SIV hosts can harness immune negative regulatory systems that temper the response to SIV, preventing the overstimulation that leads to T cell exhaustion. Regulatory T cells, which have such a negative function, may mediate this inhibition. Further elucidation of their differential action in SIV-susceptible and -resistant monkeys may point to new therapeutic approaches to reestablishing immune harmony in patients infected with HIV.

B. Jacquelin et al., Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Invest. 23 November 2009 (10.1172/JCI40093) [Full Text]

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