Affiliation:
1. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA
Abstract
Of all the accessory proteins encoded by HIV-1 and other primate lentiviruses, Vif has arguably the strongest potential as a target for antiviral therapy. This conclusion is based on the observation that replication of HIV-1
in vivo
is critically dependent on Vif. Thus, inhibiting the function of Vif via small-molecule inhibitors or other approaches has significant therapeutic potential. We previously identified dominant-negative (D/N) Vif variants whose expression interferes with the function of virus-encoded wild-type Vif. We now show that D/N interference involves competitive binding of D/N Vif variants to the transcriptional cofactor core binding factor beta (CBFβ), which is expressed in cells in limiting quantities. Overexpression of CBFβ neutralized the D/N phenotype of Vif. In contrast, overexpression of Runx1, a cellular binding partner of CBFβ, phenocopied the D/N Vif phenotype by sequestering endogenous CBFβ. Thus, our results provide proof of principle that D/N Vif variants could have therapeutic potential.
Funder
HHS | NIH | NIH Office of the Director
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
6 articles.
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