The cellular HIV-1 Rev cofactor hRIP is required for viral replication
PGraduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Gene Products, rev; HIV-1; Hela Cells; Humans; Mutation; Nuclear Pore Complex Proteins; RNA Interference; RNA-Binding Proteins; Virus Replication; rev Gene Products, Human Immunodeficiency Virus
Life Sciences | Medicine and Health Sciences
An important goal of contemporary HIV type 1 (HIV-1) research is to identify cellular cofactors required for viral replication. The HIV-1 Rev protein facilitates the cytoplasmic accumulation of the intron-containing viral gag-pol and env mRNAs and is required for viral replication. We have previously shown that a cellular protein, human Rev-interacting protein (hRIP), is an essential Rev cofactor that promotes the release of incompletely spliced HIV-1 RNAs from the perinuclear region. Here, we use complementary genetic approaches to ablate hRIP activity and analyze HIV-1 replication and viral RNA localization. We find that ablation of hRIP activity by a dominant-negative mutant or RNA interference inhibits virus production by mislocalizing Rev-directed RNAs to the nuclear periphery. We further show that depletion of endogenous hRIP by RNA interference results in the loss of viral replication in human cell lines and primary macrophages; virus production was restored to wild-type levels after reintroduction of hRIP protein. Taken together, our results indicate that hRIP is an essential cellular cofactor for Rev function and HIV-1 replication. Because hRIP is not required for cell viability, it may be an attractive target for the development of new antiviral strategies.
Rights and Permissions
Citation: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4027-32. Epub 2005 Mar 4. Link to article on publisher's site
DOI of Published Version
Proceedings of the National Academy of Sciences of the United States of America
Yu, Zhong; Sanchez-Velar, Nuria; Catrina, Irina E.; Kittler, Ellen L. W.; Udofia, Enyeneama B.; and Zapp, Maria L., "The cellular HIV-1 Rev cofactor hRIP is required for viral replication" (2005). GSBS Student Publications. 704.