The cellular HIV-1 Rev cofactor hRIP is required for viral replication
Authors
Yu, ZhongSanchez-Velar, Nuria
Catrina, Irina E.
Kittler, Ellen L. W.
Udofia, Enyeneama B.
Zapp, Maria L.
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyProgram in Molecular Medicine
PGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2005-03-08Keywords
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 VirusLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4027-32. Epub 2005 Mar 4. Link to article on publisher's siteDOI
10.1073/pnas.0408889102Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34056PubMed ID
15749819Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0408889102