Advances in SIV/SHIV Non-Human Primate Models of NeuroAIDS

Abstract

Non-human primates (NHPs) are the most relevant model of Acquired Immunodeficiency Syndrome (AIDS) and neuroAIDS, being of great importance in explaining the pathogenesis of HIV-induced nervous system damage. Simian Immunodeficiency Virus (SIV)/ Simian-Human Immunodeficiency Virus (SHIV)-infected monkeys have provided evidence of complex interactions between the virus and host that include host immune response, viral genetic diversity, and genetic susceptibility, which may explain virus-associated central nervous system (CNS) pathology and HIV-associated neurocognitive disorders (HAND). In this article, we review the recent progress contributions obtained using monkey models of HIV infection of the CNS, neuropathogenesis and SIV encephalitis (SIVE), with an emphasis on pharmacologic therapies and dependable markers that predict development of CNS AIDS.

Keywords: Simian Immunodeficiency Virus; inflammation; macaque; macrophages; markers; neuroAIDS.

Figure 1

HIV infection into the CNS. HIV can cross the BBB through HIV-1-infected CD4+ T cells or HIV-1-infected monocytes that differentiate into perivascular macrophages, becoming latently infected brain macrophages, or by direct entry, possible in the case of increased permeability. CNS cells susceptible to HIV-1 infection are microglia and astrocytes, while neurons may be damaged by neuroinflammatory processes. Abbreviations: Human Immunodeficiency Virus (HIV), blood–brain barrier (BBB), central nervous system (CNS).

Figure 2

Applications of NHP models infected with SIV/SHIV in neuroAIDS. Abbreviations: SHIV: Simian-Human Immunodeficiency Virus; SIV: Simian Immunodeficiency Virus; NHP: non-human primate; AIDS: Acquired Immunodeficiency Syndrome; ART: antiretroviral therapy; CNS: central nervous system; CSF: cerebrospinal fluid; AAV9: Adeno-Associated Virus 9; CRISP: Clustered Regularly Interspaced Short Palindromic Repeats.