Article

Nonprogressive and Progressive Primate Immunodeficiency Lentivirus Infections

Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
Immunity (Impact Factor: 21.56). 06/2010; 32(6):737-42. DOI: 10.1016/j.immuni.2010.06.004
Source: PubMed
ABSTRACT
Natural hosts for simian immunodeficiency virus (SIV) can be, and are often naturally, infected with species-specific SIVs, but do not develop acquired immunodeficiency syndrome (AIDS). These natural hosts maintain high SIV viral loads, but avoid immunodeficiency. Elucidating the mechanisms that allow natural hosts to coexist with SIV without overt disease may provide crucial information for understanding AIDS pathogenesis. Over the past few years, several key features of natural SIV infections have been described in studies conducted predominantly in sooty mangabeys (SMs), African green monkeys (AGMs), and mandrills. Natural SIV hosts are able to avoid the chronic, generalized immune system activation that is associated with disease progression in HIV-infected individuals and are known to downmodulate the expression of the receptors for SIV. In this perspective we propose that a critical factor that differentiates nonprogressive from progressive HIV or SIV infection is the maintenance of T cell immune competence in the face of a virus that infects and kills CD4(+) T cells. Elucidation of the mechanisms underlying the preservation of immune function during and after the acute phase of natural SIV infection may lead to the design of novel preventive and therapeutic interventions for treatment of chronic HIV infection.

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    • "One important observation in this regard is that there are low levels of CCR5 coreceptor expression on central memory CD4 T cells in natural SIV hosts[11,29,48].Paiardini et al.demonstrated that central memory CD4 T cells in sooty mangabey resist CCR5 upregulation following activation and were relatively resistant to infection both in vivo and in vitro[49]. Thus, restricted and delayed expression of CCR5 on activated CD4 T cells may preserve the homeostasis of the pool of " resting " naïve and memory CD4 T cells while supporting high levels of virus production in activated effector CD4 cells that are likely to die as a consequence of activation-induced cell death[31]. "
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    • "In contrast to experimental infections of Asian macaques (Macaca mulatta) with SIV, infections in natural hosts (African nonhuman primates; ie, sooty mangabeys, African green monkeys , and mandrills) are nonpathogenic [62] . While both pathogenic and nonpathogenic SIV infections are similar in the extent of viral replication and cytopathy, there is an absence of systemic chronic immune activation in nonpathogenic infections of natural hosts [62]. Factors that contribute to immune activation in HIV-1–infected individuals can be of viral origin, such as Env, Nef, Tat, and Vpr, a consequence of an ineffective resolution of antiviral innate and adaptive immune responses and/or increased permeability of the gastrointestinal epithelium to microbial products, which result in activation of the innate immune responses and enhanced production of proinflammatory cytokines, such as IFN-α, TNF-α, interleukin 1, and interleukin 6 [61]. "
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