Eradication of HIV from CNS/Myeloid Reservoirs Program

Overview

This program supports innovative research in five areas: (1) basic research to identify and characterize persistent/latent HIV-1 in cells derived from the central nervous system (CNS), such as macrophages, microglia, T-cells, and astrocytes, in the setting of suppressive antiretroviral therapy (ART); (2) basic research to determine the mechanisms involved in the temporal establishment, maintenance, and resurgence of persistent/latent HIV-1 in the CNS, particularly in relationship to the timing of antiretroviral therapy; (3) development of physiologically relevant animal models and CNS-based cellular assays that recapitulate HIV-1 persistence and latency in the presence of effective ART; (4) feasibility assessments of current and emerging eradication approaches to reactivate persistent HIV-1 from CNS-derived cells such as macrophages, microglia, T-cells, and astrocytes; and (5) assessment of CNS toxicity and adverse impacts of current and emerging eradication strategies.

Areas of Emphasis

• Identify all potential latent and persistent HIV-1 CNS cellular reservoirs.
• Discover the molecular mechanisms involved in establishment, maintenance, and resurgence of HIV-1 CNS cellular reservoirs in relationship to the timing and effects of ART.
• Elucidate mechanisms of CNS immune escape in persistently/latently infected cells in the context of ART and the role of inflammation in maintaining HIV-1 persistence in the CNS.
• Develop and adapt physiologically relevant cell-based assays and animal models to recapitulate HIV-1 persistence/latency in the presence of effective ART and to test viral eradication strategies.
• Develop novel neuroimaging approaches to discover and study cellular biomarkers that detect latently and persistently infected cells in the CNS.
• Develop innovative eradication strategies with increased blood-brain barrier permeability and CNS targeting to eliminate latent/persistent CNS reservoirs and novel silencing approaches to prevent CNS viral resurgence in upon ART cessation.
• Assess the impact of current HIV-1 eradication strategies on neuroinflammation, neurocognitive impairment, and other CNS outcomes.

Contact

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