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Gene M. Shearer, Ph.D.
Immune Dysregulation in HIV/AIDS and Natural Immunity against HIV Infection
The immune dsyregulation and pathogenesis resulting from HIV-1 infection is characterized by depletion of CD4+ T lymphocytes and by chronic pan-immune activation. As a model of HIV-induced pathogenesis, this laboratory is investigating apoptotic T cell death that is mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R). We are studying the role of noninfectious HIV-1 particles (induced by chemical treatment) for inducing pan-immune activation.
Immune protection against HIV infection is a high priority of AIDS research. A recent development in protection against HIV is the realization that soluble factors produced by leukocytes can block HIV entry or replication. The laboratory has discovered soluble factors that are induced in vitro by either infection with influenza virus (FLU) or stimulation with allogeneic leukocytes (ALLO). These factors inhibit HIV replication prior to reverse transcription, and are none of the beta-chemokines or the CD8 antiviral factor (CAF). Most of the FLU- but not of ALLO-generated HIV inhibitory activity is due to IFN-gamma. The strength of the ALLO- but not the FLU-generated HIV inhibitory activity appears to be regulated by HLA-A-linked genetics. We have recently discovered that a major component of the ALLO-stimualted factor is due to a ribonuclease. Studies are in progress to: (1) further characterize and identify the HIV inhibitory factors generated by ALLO stimulation; (2) determine the mechanism(s) of HIV inhibition; (3) determine whether these factors inhibit other viruses; (4) elucidate the HLA-A association with the regulation of ALLO-stimulated factor activity; and (5) determine whether the ribonuclease contained in the ALLO stimulated factor contributes to natural protection against vertical transmission of HIV.
Collaborating in our work are: Jean-Charles Grivel, NICHD, NIH, Bethesda, MD; Mary Carrington, NCI-Frederick, Frederick, MD; Jeff Lifson, AIDS Vaccine Program, SAIC-Frederick, Frederick, MD; Matthew Dolan, USAF Medical Center, Lackland AFB, TX; and Claire Chougnet, Childrens' Hospital Res. Fdn., Cincinnati, OH.
This page was last updated on 3/5/2013.