Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts

Abstract

To understand how natural sooty mangabey hosts avoid AIDS despite high levels of simian immunodeficiency virus (SIV) SIVsm replication, we inoculated mangabeys and nonnatural rhesus macaque hosts with an identical inoculum of uncloned SIVsm. The unpassaged virus established infection with high-level viral replication in both macaques and mangabeys. A species-specific, divergent immune response to SIV was evident from the first days of infection and maintained in the chronic phase, with macaques showing immediate and persistent T-cell proliferation, whereas mangabeys displayed little T-cell proliferation, suggesting subdued cellular immune responses to SIV. Importantly, only macaques developed CD4؉ -T-cell depletion and AIDS, thus indicating that in mangabeys limited immune activation is a key mechanism to avoid immunodeficiency despite high levels of SIVsm replication. These studies demonstrate that it is the host response to infection, rather than properties inherent to the virus itself, that causes immunodeficiency in SIV-infected nonhuman primates.

Regulation of TNF-related apoptosis-inducing ligand on primary CD4 + T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

“…Sooty mangabey monkeys do not exhibit apoptosis, CD4 ϩ T cell depletion, or an AIDS-like syndrome when infected by SIV (40). In marked contrast to rhesus macaques, which develop AIDS, pDCs from Sooty mangabey monkeys do not produce IFN-␣ when exposed to SIV.…”

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

“…Whilst induction of cell proliferation can be viewed as an indicator of preserved immune function (Sun et al, 2007), most reports instead describe a correlation with high virus load and disease progression (Hazenberg et al, 2003;Sopper et al, 2000). Furthermore, HLA-DR and Ki-67 are not increased in HIV-1-infected chimpanzees or SIV-infected sooty mangabeys, where disease development generally does not occur (Gougeon et al, 1997;Silvestri et al, 2005Silvestri et al, , 2003Sumpter et al, 2007). Here, we have reported a similar upregulation of Ki-67 in SHIV 89.6p -infected animals.…”

Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy

“…Cells derived from peripheral blood (PB) and LN were isolated by gradient centrifugation. Fourcolor flow cytometric analysis was performed according to standard procedures, using a panel of monoclonal antibodies (MAbs) that were originally designed to detect human molecules but that we and others have shown to be cross-reactive with SMs (43,44). The MAbs used included CD8-phycoerythrin (clone SK1), CD8-allophycocyanin (clone SK1), CD3-phycoerythrin (clone SP34-2), CD4-peridinin chlorophyll protein (clone L200), and Ki67-fluorescein isothiocyanate (FITC) (clone B56) (BD PharMingen, San Diego, CA) and CD14-FITC (clones RMO52 and MY4) (Beckman Coulter, Miami, FL).…”