MOLECULAR BASIS OF HIV-1 PERSISTENCE

Project: Research project

Description

Mechanisms underlying viral persistence in the course of AIDS remain one of
the more perplexing aspects of HIV-1 pathogenesis at the present time. The
chronic nature of AIDS is reflected by the ability of the virus to be
maintained in a minimally replicative state without inducing rapid host
cell cytolysis. These facts are difficult to reconcile given the properties
of HIV-1 in vitro where infection of host CD4 cells results in rapid
cytolysis and high level virus replication, thus mechanisms which restrict
or regulate virus replication play an important role in the pathogenesis of
AIDS. Our studies demonstrate two mechanisms of central importance in maintenance
of a persistent viral state in AIDS: 1. The emergence of non-cytopathic HIV-1 genotypes which are able to
persist within the host cell. 2. The activated state of the host CD4+
lymphocyte. Specific Aim A: Evaluate resting CD4+ T-lymphocytes as an HIV-1 reservoir
in AIDS. (I).Determine ability of HIV-1 to replicate in resting CD4 cells
in vitro. (II). Identify T-cell subset which harbors HIV-1 DNA in vivo and
examine state and load of a proviral DNA in AIDS patients. (III) Evaluate
opportunistic agents for ability to augment HIV-1. production from resting
T-cells in vitro. Specific Aim B: Identify the presence of noncytopathic HIV-1 genotypes in
AIDS patients which contribute to viral persistence.(I) Clone noncytopathic
viruses from HIV-1 seropositive individuals. (II). Through the construction
of chimeric viruses and DNA sequencing, delineate regions of the genome
which are important for the noncytopathic phenotype. It is proposed that these studies will provide fundamental insight into the
basis for viral persistence in AIDS and identify biologic features of the
host cell reservoir and of the virus itself which effect maintenance of the
virus in this reservoir.
StatusFinished
Effective start/end date9/1/9010/13/95

Funding

  • National Institutes of Health: $128,694.00
  • National Institutes of Health: $151,495.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $135,290.00

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HIV-1
Acquired Immunodeficiency Syndrome
Viruses
Virus Replication
Genotype
DNA
T-Lymphocyte Subsets
DNA Sequence Analysis
Maintenance
T-Lymphocytes
Clone Cells
Lymphocytes
Phenotype
Infection

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)