Non-human primate models of SIV infection and CNS neuropathology

Abstract

Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulated immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages. Consistent in all of these models are data underscoring the importance of monocyte and macrophage activation, infection and accumulation in the CNS.

The dynamics of simian immunodeficiency virus after depletion of CD8+ cells

“…Another common use is in a model of SIV‐induced encephalitis (SIVE). Depletion of CD8+ cells in primary infection leads to high viral loads and rapid progression, including a high incidence of SIVE, more than double in comparison to infection in nondepleted animals …”

“…Depletion of CD8+ cells in primary infection leads to high viral loads and rapid progression, including a high incidence of SIVE, more than double in comparison to infection in nondepleted animals. [60][61][62] Here we focus on studies of CD8+ cell depletion during chronic infection, because some of these experiments have been analyzed in more detail through modeling. As schematically shown in Figure 1B, administration of a CD8-depleting antibody during chronic infection leads to a profound depletion of CD8+ cells in the periphery, although depletion at other sites, such as lymph node and mucosa, is usually less pronounced and more variable.…”

SIV Latency in Macrophages in the CNS

“…SIV infection in macaques comprehensively reproduces the immunodeficiency symptoms observed in HIV-infected humans, with infection of CD4+T cells and monocytes in blood, and of macrophages in tissues such as lymph nodes, bowel, brain, lung, spleen, and heart (81, 82). Antiretroviral drugs have been shown to fully suppress SIV replication in blood (82) and, in limited studies, CSF (83–85) to levels comparable to those in ART-suppressed HIV-infected individuals.…”

“…The most commonly used strains are cloned SIVmac239 and SIVmac251 strains, or viruses derived from these strains. Also, there are SIV models focused on the study of infection and disease progression in the CNS (81). Each model uses distinct mechanisms to achieve SIV encephalitis, which includes infecting macaques with naturally occurring neurotropic and immunosuppressive virus swarms, neurotropic virus adapted by in vivo passage of SIV, and non-neurotropic strains in association with CD8+ lymphocyte depletion (81).…”

“…Also, there are SIV models focused on the study of infection and disease progression in the CNS (81). Each model uses distinct mechanisms to achieve SIV encephalitis, which includes infecting macaques with naturally occurring neurotropic and immunosuppressive virus swarms, neurotropic virus adapted by in vivo passage of SIV, and non-neurotropic strains in association with CD8+ lymphocyte depletion (81). A recent review has compared these SIV models concluding that all the models include monocyte/macrophage infection and activation, and increased number of macrophages in the brain of macaques that develop encephalitis (81).…”