The anti-viral protein of trichosanthin penetrates into human immunodeficiency virus type 1

Trichosanthin (TCS) is a type I ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus type 1, and has been clinically applied in acquired immunodeficiency syndrome (AIDS) therapy. Previous studies revealed that TCS recognized human immunodeficiency virus type 1 (HIV-1) particles. Here, we investigated the physical relationship between TCS and HIV-1 particles, and demonstrated that TCS penetrates into viral particles, where it is protected from various protease digestion. The penetration of TCS exerts no obvious effect on viral integrity. FYY140–142, D176, and K177 were identified as key amino acid residues for the membranetranslocation process. Moreover, TCS penetrated into HIV-1 virions showed potent anti-viral activity. Overall, the observations suggest that the penetration of TCS into HIV-1 particles may be important for eliminating the virus.