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Viral and Host Genetic Factors Regulating HIV-Associated CNS Disease

NAMHC Concept Clearance

Presenter

Jeymohan Joseph, Ph.D.
HIV Neuropathogenesis Program
Center for Mental Health Research on AIDS
Division of AIDS and Health Behavior Research

Goal

This initiative will support research on viral and host genetic factors regulating susceptibility to and progression of HIV-associated neurologic and neuropsychiatric disease.

Rationale

Recent technological advances in genetics have substantially improved our capability for understanding the role of genetic factors in the pathophysiology of various disease states. The NIH Office of AIDS Research is also seeking to leverage genetics and genomics resources for the study of HIV/AIDS and has identified this as an important priority area. There is currently a remarkable opportunity to conduct genetic studies with the availability of specimen resources from large NIH-funded HIV related studies such as Multi-center AIDS Cohort Study (MACS) , Women’s Interagency HIV Study (WIHS), CNS HIV Antiretroviral Therapy Effects Research (CHARTER), and the National NeuroAIDS Tissue Consortium (NNTC). This initiative will be timely because of the critical need to understand the genetic basis of susceptibility to HIV-associated central nervous system (CNS) disease and the availability of novel technologies and specimen resources to conduct such studies.

The initiative would encourage research in two broad areas

I. Viral Genetics

Areas of Emphasis:

  1. Analysis of HIV sequences that facilitate neurotropism and infection of various subpopulations of cells (microglia, astrocytes) in the CNS; research utilizing HIV sequence analysis to address emerging questions in the areas of viral trafficking, compartmentalization, regional infection, viral evolution and establishment of CNS reservoirs; the evaluation of HIV genetic heterogeneity and impact on functional effects in the CNS; and research on emergence of drug resistance mutations in the CNS vs. periphery in the setting of potent anti-retroviral therapy.
  2. The impact of viral genetic diversity (clade diversity) on HIV neuropathogenesis from a global perspective; studies comparing the ability of different HIV subtypes to cause neurologic and neuropsychiatric disease; and the mechanisms that regulate clade differences in the manifestation of HIV-associated CNS.

II. Host Genetics

Areas of Emphasis:

Research on the relationship between host genetics and susceptibility and disease progression of HIV-associated neurologic and neuropsychiatric disease; the use of new approaches (Genome Wide Association Studies) and resources (International HapMap project); and the role of gene-environment interactions and epigenetic factors that influence pathogenesis of HIV-associated central nervous system disease.

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