Authors
Nathans, Robin S.Cao, Hong
Sharova, Natalia
Ali, Akbar
Sharkey, Mark E.
Stranska, Ruzena
Stevenson, Mario
Rana, Tariq M.
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2008-09-23Keywords
Anti-HIV AgentsCytidine Deaminase
Cytosine Deaminase
HIV Infections
HIV-1
Humans
Immunity, Innate
vif Gene Products, Human Immunodeficiency Virus
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The HIV-1 protein Vif, essential for in vivo viral replication, targets the human DNA-editing enzyme, APOBEC3G (A3G), which inhibits replication of retroviruses and hepatitis B virus. As Vif has no known cellular homologs, it is an attractive, yet unrealized, target for antiviral intervention. Although zinc chelation inhibits Vif and enhances viral sensitivity to A3G, this effect is unrelated to the interaction of Vif with A3G. We identify a small molecule, RN-18, that antagonizes Vif function and inhibits HIV-1 replication only in the presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner and increases A3G incorporation into virions without inhibiting general proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in the presence of A3G, reduces viral infectivity by increasing A3G incorporation into virions and enhances cytidine deamination of the viral genome. These results demonstrate that the HIV-1 Vif-A3G axis is a valid target for developing small molecule-based new therapies for HIV infection or for enhancing innate immunity against viruses.Source
Nat Biotechnol. 2008 Oct;26(10):1187-92. Epub 2008 Sep 21. Link to article on publisher's site
DOI
10.1038/nbt.1496Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39193PubMed ID
18806783Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/nbt.1496