Abstract
HIV-associated neurocognitive disorders (HAND) continue to affect a large proportion of HIV-1-infected individuals. The results of over two decades of research into delineating the neuropathogenesis of HAND underscore the role of inflammation, oxidative stress, excitotoxicity, and other pathogenic processes driven largely by host immune responses to viral presence. Host genotype, which largely determines host immune response, has proven an important factor in HIV infectivity and disease progression but has proven less useful for understanding HAND neuropathogenesis. Dynamic molecular genetic processes, including gene expression and epigenetics, may be even more applicable to HAND, in which symptoms wax and wane over time. In this chapter we summarize the current state of understanding of host genomic, transcriptomic, and epigenomic factors associated with HAND. We also discuss challenges and suggest some priorities for future research, including the need for (1) longitudinal studies using consistent phenotypic definitions of HAND; (2) focus on understudied populations such as children; (3) studies that correlate neuropathological or neurophysiological changes in multiple brain regions with genomic markers in affected individuals and with changes at the RNA, epigenomic, and/or protein levels; and (4) movement toward development of more reliable and valid phenotypes of HAND.
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Acknowledgments
Dr. Levine – NIH R21 MH107327-01 (Levine and Hoare), R21AG046954 (Horvath and Levine), R01MH096648 (Levine and Moore), R01DA030913 (Levine and Horvath), R03DA026099 (Levine), California HIV-AIDS Research Program ID06-LA-187 (Levine), UCLA-AIDS Institute, and the UCLA Center for AIDS Research AI28697 (Freimer and Levine).
Dr. Kallianpur – NIH R01 MH095621 (To A. Kallianpur and T. Hulgan).
Dr. Singh – NIH R01 (MH085608), R03 (MH103995), and California HIV/AIDS Research Program IDEA Grant (ID07-SD-160) (To K.K. Singh).
Conflict of interest The authors report no conflicts of interest.
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Levine, A.J., Singh, K.K., Kallianpur, A.R. (2017). Genetic, Epigenetic, and Transcriptomic Studies of NeuroAIDS. In: Shapshak, P., et al. Global Virology II - HIV and NeuroAIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7290-6_19
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