Contribution of Host Nucleoporin 62 in HIV-1 Integrase Chromatin Association and Viral DNA Integration

• Published in: The Journal of biological chemistry 2012-03, Vol.287 (13), p.10544-10555
• Main Authors: Ao, Zhujun, Jayappa, Kallesh Danappa, Wang, Binchen, Zheng, Yingfeng, Wang, Xiaoxia, Peng, Jinyu, Yao, Xiaojian
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Chromatin; Chromatin Association; DNA, Viral - genetics; DNA, Viral - metabolism; Gene Knockdown Techniques; HEK293 Cells; HIV Infections - genetics; HIV Infections - metabolism; HIV Integrase - genetics; HIV Integrase - metabolism; HIV-1; HIV-1 - enzymology; HIV-1 - genetics; Humans; Integrase; Integration; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Microbiology; Nuclear Pore; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Nucleoporin 62; Protein-Protein Interaction; Retrovirus; RNA Interference (RNAi); Transcription Factors - genetics; Transcription Factors - metabolism; Virus Integration - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.317057

HIV-1 integration is promoted by viral integrase (IN) and its cellular cofactors. The lens epithelium-derived growth factor (LEDGF/p75), an IN interacting cellular cofactor, has been shown to play an important role in HIV-1 chromatin targeting and integration. However, whether other cellular cofactors are also involved in viral replication steps is still elusive. Here, we show that nucleoporin 62 (Nup62) is a chromatin-bound protein and can specifically interact with HIV-1 IN in both soluble nuclear extract and chromatin-bound fractions. The knockdown of Nup62 by shRNA reduced the association of IN with host chromatin and significantly impaired viral integration and replication in HIV-1-susceptible cells. Furthermore, the expression of the IN-binding region of Nup62 in CD4+ T cells significantly inhibited HIV-1 infection. Taken together, these results indicate that the cellular Nup62 is specifically recruited by HIV-1 IN and contribute to an efficient viral DNA integration. HIV-1 integration is promoted by viral integrase and its cellular cofactors. Nucleoporin 62 interacts with HIV-1 integrase in chromatin, and shRNA knockdown of nucleoporin 62 was able to impair integrase chromatin association and viral replication. Interaction of nucleoporin 62 and HIV-1 integrase contributes to viral DNA integration. A new nucleoporin was identified as an integrase-binding cofactor required for HIV-1 integration and replication.