New Insight Into HIV Infection
When HIV infects a cell, it carries its DNA into the nucleus of the cell, then the viral DNA mixes with the cell’s DNA. The combined DNA produces proteins that make new viruses, which spread to neighboring cells. The mechanism by which HIV’s DNA enters the nucleus is not yet fully understood and may offer new ways to fight HIV.
Xiaojian Yao and colleagues studied how the virus uses various proteins of the infected cell in order to enter the nucleus. They revealed new roles for these proteins that had not been fully established. The study also showed that by hindering the virus to interact with those proteins, or by silencing genes that produce one of these proteins, HIV was three times less infectious than when the protein was present.
J Biol Chem. 2007 May 4;282(18):13456-67. Epub 2007 Mar 14.
Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication.
Ao Z, Huang G, Yao H, Xu Z, Labine M, Cochrane AW, Yao X.
Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0W3.
Similar to all other viruses, human immunodeficiency virus type 1 (HIV-1) depends heavily on cellular factors for its successful replication. In this study we have investigated the interaction of HIV-1 integrase (IN) with several host nuclear import factors using co-immunoprecipitation assays. Our results indicate that IN interacts specifically with host importin 7 (Imp7) in vivo, but does not interact with importin 8 (Imp8) or importin alpha (Rch1). In contrast, another HIV-1 karyophilic protein MAp17, which is capable of binding Rch1, fails to interact with Imp7, suggesting that IN and Map17 may interact with different cellular pathways during HIV-1 replication. Genetic analysis revealed that the C-terminal domain of IN is the region responsible for interaction between IN with Imp7, and an IN mutant (K240A,K244A/R263A,K264A) disrupted the Imp7 binding ability of the protein, indicating that both regions ((235)WKGPAKLLWKG and (262)RRKAK) within the C-terminal domain of IN are required for efficient IN/Imp7 interaction. Using a vesicular stomatitis virus G glycoprotein pseudotyped HIV single-cycle replication system, we showed that the IN/Imp7 interaction-deficient mutant was unable to mediate viral replication and displayed impairment at both viral reverse transcription and nuclear import steps. Moreover, transient knockdown of Imp7 in both HIV-1 producing and target cells resulted in a 2.5-3.5-fold inhibition of HIV infection. Altogether, our results indicate that HIV-1 IN specifically interacts with Imp7, and this viral/cellular protein interaction contributes to efficient HIV-1 infection.
PMID: 17360709 [PubMed – in process]