Viral and Host Genetics Program

Overview

This program supports basic and clinical research to determine the viral and host genetic factors involved in central nervous system (CNS) impairment caused by HIV-1 worldwide, both of which contribute to pathophysiology of HIV-1-associated CNS dysfunction. New genetic technologies can enhance our understanding of pathophysiological mechanisms and aid in the development of innovative strategies for discovery of therapeutic drug targets. The program encourages the use of state-of-the-art approaches (e.g., transcriptomics, phenomics, epigenomics, whole genome association studies, next generation sequencing, single cell technologies, and systems biology) to identify and validate viral and host genetic factors that influence the pathophysiology of HIV-1-associated CNS dysfunction.

Areas of Emphasis

Viral Genetics

• Study the role of HIV-1 sequence diversity in neurovirulence, neurotropism, discordant and compartmentalized viral evolution, CNS cell type-specific infection, regional genetic heterogeneity, and associated functional effects.
• Examine molecular and genetic mechanisms of potential subtype/clade differences in HIV-1 neuropathogenesis.
• Identify viral genetic signatures associated with HIV-1-induced CNS dysfunction.
• Study the role of viral epigenetic factors in the pathophysiology of HIV-1-associated CNS dysfunction.
• Investigate the role of viral and host transcriptional regulation (including viral protein modifications, histone modifications, changes in chromatin structure, and non-coding RNA) in HIV-1 neuropathogenesis.

Host Genetics

• Examine the role of host genetic factors, including epigenetic mechanisms, in regulating susceptibility to HIV-1-associated CNS dysfunction.
• Assess epigenetic host responses to viral infection mediated through chromatin modification, non-coding RNAs, and DNA methylation.
• Study host genetic factors involved in regulating responsiveness to antiretroviral therapy and neuroprotective adjuvant therapies (pharmacogenomics).
• Delineate the genetic basis of host restriction factors that regulate HIV-1 replication in different CNS cell types.

Contact

Jeymohan Joseph, Ph.D.
5601 Fishers Lane, Room 9G20
Rockville, MD 20852
240-627-3869, jjeymoha@mail.nih.gov