Contribution of host nucleoporin 62 in HIV-1 integrase chromatin association and viral DNA integration

宿主核孔蛋白 62 对 HIV-1 整合酶染色质结合和病毒 DNA 整合的贡献

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作者:Zhujun Ao, Kallesh Danappa Jayappa, Binchen Wang, Yingfeng Zheng, Xiaoxia Wang, Jinyu Peng, Xiaojian Yao

Abstract

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.

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