SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase

Abstract

SIV-infected natural hosts do not progress to clinical AIDS yet display high viral replication and an acute immunologic response similar to pathogenic SIV/HIV infections. During chronic SIV infection, natural hosts suppress their immune activation, whereas pathogenic hosts display a highly activated immune state. Here, we review natural host SIV infections with an emphasis on specific immune cells and their contribution to the transition from the acute-to-chronic phases of infection.

Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys

“…It is now evident that the majority of the initial acute-phase immune activation events in SIV-infected natural host species resolve during the transition from acute to chronic phase, which generally occurs later, around 21 to 28 days postinfection (5,14,18,22,26,33). Therefore, down-modulating the LPS-specific monocyte TNF-␣ response in SIV-infected SM may be an early step in establishing the low levels of immune activation observed during the chronic phase of the infection.…”

“…However, a key difference between pathogenic and nonpathogenic infections is the ability to resolve early increases in immune activation. In SIV-infected natural hosts, the early induction of immune activation during the acute phase of infection is transient, and the chronic stage of infection (after 4 weeks) is characterized by low levels of systemic immune activation as determined by cytokine and chemokine levels in peripheral blood and the activation state of multiple immune cell subsets (5,22,33). It is clear that the ability to restrict chronic immune activation is a critical component of a nonpathogenic disease outcome in SM (37,46,48), and elucidating the mechanisms underlying this phenotype will have important implications for understanding and treating the pathogenesis of HIV disease.…”

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

“…1 Recently, it has been accepted that in addition to the direct infection of CD4 1 T lymphocytes by HIV virions, chronic immune activation in HIV-infected human and simian immunodeficiency virus (SIV)-infected non-natural hosts, such as rhesus macaques and cynomolgus macaques, may greatly contribute to the pathogenesis of AIDS. [2][3][4][5][6][7] Accumulated evidence suggests that large amounts of type I interferons (IFNs) produced by activated plasmacytoid dendritic cells (pDCs) might play a critical role in this chronic immune activation during HIV-1 infection. Clinical strategies aimed at inhibiting pDC activation could effectively counter disease progression in HIV patients.…”

HIV Without AIDS: The Immunological Secrets of Natural Hosts

“…One might hypothesize that in sooty mangabeys, preservation of CD4 T cell homeostasis in the peripheral blood compensates for the loss of mucosal CD4 T cells, and is sufficient to maintain a functional immune system. This hypothesis, however, is not consistent with the observation that a fraction of naturally and experimentally infected sooty mangabeys experience a variable but significant (with animals showing <100 cells/ul blood) loss of CD4 T cell in blood and tissues, while still remaining healthy and AIDS-free Mir, Gasper, Sundaravaradan, & Sodora, 2011;Sumpter et al, 2007;Taaffe et al, 2010). The evidence indicates that even a generalized depletion of CD4 T cells, per se, is not sufficient to induce progression to AIDS in natural hosts for SIV.…”