[Human Rev-interacting protein (hRIP) as a target]
>>Published online before print March 4, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0408889102
OPEN ACCESS ARTICLE
Cell Biology
The cellular HIV-1 Rev cofactor hRIP is required for viral replication
( Rev-directed RNA export | RNA localization )
Zhong Yu, Nuria Sánchez-Velar, Irina E. Catrina, Ellen L. W. Kittler, Enyeneama B. Udofia, and Maria L. Zapp *
Program in Molecular Medicine and Center for AIDS Research (CFAR), University of Massachusetts Medical School, Worcester, MA 01605
Edited by Keith R. Yamamoto, University of California, San Francisco, CA, and approved January 22, 2005 (received for review November 30, 2004)
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.<<
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