High Levels of Viral Replication during Primary Simian Immunodeficiency Virus SIVagm Infection Are Rapidly and Strongly Controlled in African Green Monkeys

Abstract

In contrast to pathogenic human immunodeficiency virus and simian immunodeficiency virus (SIV) infections, chronic SIVagm infections in African green monkeys (AGMs) are characterized by persistently low peripheral and tissue viral loads that correlate with the lack of disease observed in these animals. We report here data on the dynamics of acute SIVagm infection in AGMs that exhibit remarkable similarities with viral replication patterns observed in peripheral blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication led by days 7 to 10 to peak viremias characterized by high levels of antigenemia (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (104 to 105 DNA copies/106 peripheral blood mononuclear cells [PBMC]), and plasma RNA viral load (2 × 106 to 2 × 108 RNA copies/ml). The lymph node (LN) RNA and DNA viral load patterns were similar to those in blood, with peaks observed between day 7 and day 14. These values in LNs (ranging from 3 × 105 to 3 × 106 RNA copies/106LN cell [LNC] and 103 to 104 DNA copies/106 LNC) were at no time point higher than those observed in the blood. Both in LNs and in blood, rapid and significant decreases were observed in all infected animals after this peak of viral replication. Within 3 to 4 weeks p.i., antigenemia was no longer detectable and peripheral viral loads decreased to values similar to those characteristic of the chronic phase of infection (102to 103 DNA copies/106 PBMC and 2 × 103 to 2 × 105 RNA copies/ml of plasma). In LNs, viral loads declined to 5 × 101 to 103 DNA copies and 104 to 3 × 105 RNA copies per 106 LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 × 104 RNA copies/106 LNC). Despite extensive viremia during primary infection, neither follicular hyperplasia nor CD8+ cell infiltration into LN germinal centers was detected. Altogether, these results indicate that the nonpathogenic outcome of SIVagm infection in its natural host is associated with a rapidly induced control of viral replication in response to SIVagm infection, rather than with a poorly replicating virus or a constitutive host genetic resistance to virus replication.

Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence

“…sab92018 (4,32,33). SIVagm.sab naturally infects sabaeus AGMs from Senegal (32). Similar to other SIVagm.sab strains (51), strain SIVagm.sab92018 is dual tropic, using both CCR5 and CXCR4 coreceptors (4).…”

“…SIV infections in their natural African non-human primate hosts are characterized by 1) active viral replication, with set-point levels similar, or even higher than those reported in pathogenic infection (2-10); 2) transient depletion of peripheral CD4 ϩ T cells during primary infection that rebound to preinfection levels during the chronic stage (3,4,7,9,10,32,33); and 3) transient and moderate increases in immune activation and proliferation during acute infection, with return to baseline levels during the chronic phase (2)(3)(4)(5)(6)(7)(8)(9)(10). Altogether, the action of all these factors results in an active persistent infection, which generally has no deleterious consequences on the natural hosts of SIV.…”

A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 + T cell depletion in SHIV-infected macaques

“…Although these data do not totally rule out the possibility that other factors contribute to CD4 ϩ T cell depletion, they strongly support the hypothesis that the 3S viral peptide plays a major role in the immune depression of HIV and SHIV infection. They may provide insight to improve our understanding of the lack of pathogenicity of natural SIV lentivirus infection in African green monkeys, a pathogenic lentivirus to the natural host, and the different factors that might control viral burden and pathogenicity (23,24).…”

Simian-Human Immunodeficiency Viruses and Their Impact on Non-Human Primate Models for AIDS

“…In addition, while humoral immune responses are mounted during SIV infection, these are relatively minimal as demonstrated by the detection of low neutralizing antibody titers in SIV-infected sooty mangabeys and AGM [15,16]. This immunologic attenuation collectively contributes to limited T-cell apoptosis and maintenance of peripheral CD4+ T-cells even though viral loads comparable to those in pathogenic SIV infection are observed [17][18][19]. The precise mechanism that triggers the downregulated immune response is unclear, but is likely to involve a combination of proposed processes that include, (1) enhanced responses of immunosuppressive regulatory T-cells and IL-17 producing Th17 cells (2) a robust early innate immune response that is swiftly constrained, and (3) controlled regulation of cellular factors or receptors associated with activation, apoptosis, or virus binding [20][21][22][23][24][25][26][27][28][29][30][31][32].…”