Neurologic impairment is now a well-recognized symptom of the acquired immunodeficiency syndrome (AIDS); many of the central nervous system (CNS) abnormalities appear to be a direct result of infection of cells of the mononuclear phagocyte lineage by human immunodeficiency virus type 1 (HIV- 1). These cells are susceptible to productive infection by some but not all HIV-1 isolates. It is of importance to identify the viral function(s) responsible for the observed differences in HIV-1 cellular tropism. The overall goal of the proposed research is to understand the mechanism of HIV-1 tropism for mononuclear phagocytes. REplication of a cloned macrophage-tropic cells, reverse transcription, integration, and virus- specific RNA production in peripheral blood lymphocytes and mononuclear phagocytes. These properties will be compared with those of HIV-1 isolates having differing abilities to productively infect mononuclear phagocytes in order to identify the stages of the HIV-1 life-cycle blocked in infection with non-tropic isolates (Aim 1). To identify viral genes or sequences responsible for mononuclear phagocyte tropism, molecular recombinants will be constructed between cloned isolates with differing abilities to replicate in these cells (Aim 2). Preliminary experiments using parental and recombinant HIV-1 strains suggest that HIV-1 strains unable to productively infect mononuclear phagocytes appear to be blocked at entry. Binding and penetration assays (Aim 3) will be used to delineate how entry is involved in infection with strains poorly tropic for mononuclear phagocytes. An understanding of precise viral mechanisms for tropic effects of HIV-1 in mononuclear phagocytes will suggest strategies to interfere with virus replication in these cells. Studies such as these may allow one to interfere with the entry of HIV-1 from the blood into the CNS via mononuclear phagocytes and reach the ultimate goal of reducing the prevalence of neurologic complications of AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI029894-03
Application #
3455564
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1990-07-01
Project End
1995-04-30
Budget Start
1992-07-01
Budget End
1993-04-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095