Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

Abstract

Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P ‫؍‬ 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P ‫؍‬ 0.7953 and P ‫؍‬ 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4 ؉ T cell depletion, as CD4 ؉ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.

Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

“…Plasma viral RNA levels were determined by RT-PCR from SIVmac239-inoculated PTM as previously described (24).…”

Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

“…To directly address the effect of microbial translocation on driving immune activation and inflammation, here we used a complimentary approach, consisting of binding LPS in the gut of a nonhuman primate pathogenic host that consistently develops gut immune dysfunction and microbial translocation during SIV infection (9,12,13). To this end, we used SIVsab-infected pigtailed macaques (PTMs), a new animal model of pathogenic SIV infection developed in our laboratory.…”

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

“…SIVmac-infected pigtail macaques tend to progress rapidly to AIDS and can potentially develop thrombocytopenia [136] which is a common autoimmune disease that can also manifest in untreated HIV-1 infected individuals. Pigtail macaques in some breeding colonies may exhibit certain pre-existing immunologic conditions such as compromised mucosal integrity, increased microbial translocation and lower levels of naïve and central memory CD4+ T-cells,have been described [34,73]. SIV/SHIV infected pigtail macaques also exhibit considerable variability in set point viral loads which is a trend that is noted in HIV-1 infected humans.…”