Mammalian cells resist virus infections through the collection of mechanisms termed innate or intrinsic immunity. One such mechanism consists of a family of cytidine deaminases termed APOBEC3. These enzymes serve as mutators that destroy the genetic material of viruses such as HIV. HIV encodes a protein of its own, termed virion infectivity factor (Vif), that binds to APOBEC3 causing its degradation. We have focused on the mechanism by which APOBEC3 and Vif function and the species specificity of the interaction. We are also developing methods to identify small molecule inhibitors that disrupt the interaction. HIV encodes a second protein, viral protein R (VPR), that is involved in inducing the degradation of several host cell proteins and that may be a second means by which HIV counteracts intrinsic immunity. Vpr binds to a chromatin-associated E3 ubiquitin ligase consisting of DDB1/CUL4A/ROC1 through the DDB1 Cullin associated factor 1 (DCAF1). The complex degrades several host proteins. We are investigating the role of this complex in HIV replication and pathogenesis and how the Vpr controls affects its function.
Professor, Department of Microbiology
PhD from Massachusetts Institute of Technology
Fellowship, University of California, San Francisco, Cancer Research
Fellowship, Massachusetts Institute of Technology
Interferon epsilon protects primary macrophages against HIV infection [Meeting Abstract]
Journal of immunology (1950). 2017 May; Conference:(104th):
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