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Peptide Inhibitors of HIV-1 Virus Infection Based on Cullin-5


  Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed innonpermissivecells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authorstook sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity innonpermissivecells with a dose-responsive manner, but not inpermissivecells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.……   
[关键词]:HIV-1 inhibitor;Peptide;Vif;Cullin-5;APOBEC3G
[文献类型]:期刊
[文献出处]: 《Chemical Research in Chinese Universities2008年03期
[格式]:PDF原版; EPUB自适应版(需下载客户端)