Animal models of HIV-associated disease of the central nervous system

It is difficult to study the pathogenesis of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) in living patients because central nervous system (CNS) tissues are only available post mortem. Rodent and nonhuman primate (NHP) models of HAND allow for longitudinal analysis of HIV-associated CNS pathology and efficacy studies of novel therapeutics. Rodent models of HAND allow for studies with large sample sizes, short duration, and relatively low cost. These models include humanized mice used to study HIV-associated neuropathogenesis and transgenic mice used to study neurotoxic effects of viral proteins without infection. Simian immunodeficiency virus (SIV)-infected NHP are the premier model of neuroAIDS; SIV-associated CNS pathology is similar to HIV-associated CNS pathology with HAND. Additionally, the size, lifespan of NHP, and time to acquired immune deficiency syndrome (AIDS) progression make SIV-infected NHP models optimal for studies of viral latency and reservoirs, and assessing novel therapeutics for neuroAIDS. NHP models of neuroAIDS generally include conventional progressors (AIDS within 2-3 years) and those that have rapid disease (AIDS within 150 days). Rapid AIDS models are achieved by immune modulation and/or infection with neurovirulent and neurosuppressive viral strains and result in a high incidence of SIV-associated encephalitis. In this chapter, we briefly review rodent and NHP models of neuroAIDS, including contributions made using these models to our understanding of HIV-associated CNS disease.