Trichosanthin inhibits integration of human immunodeficiency virus type 1 through depurinating the long-terminal repeats.
Trichosanthin (TCS) is a type I ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus type 1. However, the anti-viral mechanism remains elusive. By a well-accepted HIV-1 integration assay, we demonstrated that TCS prevents HIV-1 DNA integration in a dose dependent manner in cell culture. At the same condition, TCS fails to induce obvious cytotoxicity and is also unable to interference viral early events such as viral entry, uncoating or reverse transcription. The HIV-1 integrase can integrate HIV-1 long-terminal repeats into cellular chromosome. The interaction of TCS with these viral integration components was also examined, indicating that TCS does not interact with HIV-1 integrase by the GST-pull down assay, but binds to the long terminal repeats in a transient manner. We further revealed that TCS can efficiently depurinate HIV-1 long-terminal repeats, which may be responsible for the inhibitory activity on HIV-1 integration. In conclusion, we elucidated that TCS specifically inhibits HIV-1 integration by depurinating the long-terminal repeats.
Zhao
Wen-Long
WL
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, 100084, Beijing, People's Republic of China.
Feng
Du
D
Wu
Ju
J
Sui
Sen-Fang
SF
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045647:DNA Glycosylases / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D011687:Purines / Q000378:metabolism*; D020079:Terminal Repeat Sequences / Q000235:genetics*; D015978:Trichosanthin / Q000494:pharmacology*; D016662:Virus Integration / Q000187:drug effects*
D004279:DNA, Viral; D011687:Purines; D015978:Trichosanthin; D045647:DNA Glycosylases