Cellular protein TTRAP interacts with HIV-1 integrase to facilitate viral integration.
TTRAP is a PML-NB protein that is involved in the NF-kappaB 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.
Zhang
Jian-qi
JQ
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, China.
Wang
Jing-jing
JJ
Li
Wen-juan
WJ
Huang
Lu
L
Tian
Ling
L
Xue
Jing-lun
JL
Chen
Jin-zhong
JZ
Jia
William
W
D002460:Cell Line; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D019427:HIV Integrase; D010727:Phosphoric Diester Hydrolases; C474866:TDP2 protein, human; C514801:p31 integrase protein, Human immunodeficiency virus 1