Cellular protein TTRAP interacts with HIV-1 integrase to facilitate viral integration |
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Authors: | Jian-qi Zhang Wen-juan Li Ling Tian Jin-zhong Chen William Jia |
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Institution: | a State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, China b Department of Surgery, University of British Columbia, Vancouver, Canada |
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Abstract: | TTRAP is a PML-NB protein that is involved in the NF-κB signaling pathway. TTRAP was recently identified by yeast two-hybrid analysis as a HIV-1 integrase (HIV-1 IN) interacting protein. This interaction was verified by co-immunoprecipitation, GST pull-down, and intracellular imaging, and deletion assays suggested that the N-terminal 180 residues of TTRAP are responsible for the interaction. In stable TTRAP knock-down cell lines, the integration of viral vectors decreased significantly compared with non-silenced cell lines. Conversely, overexpression of TTRAP by transient transfection increased the percentage of integration events. This is the first time that TTRAP has been shown to interact with HIV-1 IN and facilitate lentiviral vector integration. These findings reveal a new function of TTRAP and expand our understanding of the cellular response to HIV infection. The interaction between TTRAP and HIV-1 IN may be useful in designing new anti-viral strategies as well as for improving the efficiency of lentiviral-vector-mediated gene delivery. |
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Keywords: | TTRAP HIV-1 integrase Lentivirus Integration |
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