Michael D. Powell, Ph.D.
Assistant Professor, Department of Microbiology, Biochemistry and Immunology
Nef is
known to enhance the pathogenicity of HIV-1 isolates. Deletions of nef have
also been associated with attenuation of viral pathogenesis in both humans
and primates. One feature of Nef's influence on pathogenicity is its ability
to downregulate CD4 and MHC on the cell surface. Another key aspect of Nef's
modulation of pathogenicity is its ability to influence the intrinsic infectivity
of viral particles. The increase in infectivity of Nef (+) viruses is mirrored
by an increase in the production of proviral DNA. Deletions of nef result
in a reduction in the efficiency of proviral DNA formation. While our understanding
of CD4 and MHC downregulation is fairly comprehensive, the mechanisms involved
in the enhancement of viral infectivity are basically unknown. In this study
we are interested in understanding how Nef is able to influence proviral DNA
formation and virion infectivity. We are using a combination of biochemical
and
genetic approaches to help understand the mechanisms involved. In one approach
we are looking for specific interactions of Nef with other viral and cellular
proteins to better understand the interactions going on at the molecular level.
In another approach we are doing mutagenesis on the Nef protein to better
understand the structure-function relationships of Nef. Since Nef plays a
crucial role in the pathogenesis of HIV-1 a better understanding of the function
of Nef will give us new and valuable insights into viral disease and potential
therapies.
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