Anti-HIV-1 property of trichosanthin correlates with its ribosome inactivating activity.
Trichosanthin (TCS) is a type I ribosome inactivating (RI) protein possessing anti-tumor and antiviral activity, including human immunodeficiency virus (HIV). The mechanism of these actions is not entirely clear, but is generally attributed to its RI property. In order to study the relationship between the anti-HIV-1 activity of TCS and its RI activity, three TCS mutants with different RI activities were constructed by using site-directed mutagenesis. The anti-HIV-1 activities of the three mutants were tested in vitro. Results showed that two TCS mutants, namely TCS(M(120-123)), TCS(E160A/E189A), with the greatest decrease in RI activity, lost almost all of the anti-HIV activity and cytopathic effect. Another mutant TCS(R122G), which exhibited a 160-fold decrease in RI activity, retained some anti-HIV activity. The results from this study suggested that RI activity of TCS may have significant contribution to its anti-HIV-1 property.
Wang
Jian Hua
JH
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, PR China.
Nie
Hui Ling
HL
Tam
Siu Cheung
SC
Huang
Hai
H
Zheng
Yong Tang
YT
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects*; D009154:Mutation; D011817:Rabbits; D012270:Ribosomes / Q000187:drug effects*; D015978:Trichosanthin / Q000235:genetics / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015978:Trichosanthin