Huwel, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity

作者：Yamamoto Seiji P; Okawa Katsuya; Nakano Takashi; Sano Kouichi; Ogawa Kanako; Masuda Takao; Morikawa Yuko; Koyanagi Yoshio; Suzuki Youichi^*

来源：Microbes and Infection, 2011, 13(4): 339-349.

DOI：10.1016/j.micinf.2010.12.002

• HIV-1
• MoMLV
• Integrase
• Huwe1
• Gag-Pol precursor protein

Integration, an indispensable step for retrovirus replication, is executed by integrase (IN), which is expressed as a part of a Gag-Pol precursor. Although mechanistic detail of the IN-catalyzed integration reaction is well defined, numerous evidence have demonstrated that IN is involved in multiple steps of retrovirus replication other than integration. In this study, Huwel, a HECT-type E3 ubiquitin ligase, was identified as a new cellular interactor of human immunodeficiency virus type I (HIV-1) IN. The interaction was mediated through the catalytic core domain of IN and a wide-range region of Huwel. Interestingly, although depletion of Huwel in target cells did not affect the early phase of HIV-1 infection in a human T cell line, we found that infectivity of HIV-1 released from the Huwel knockdown cells was significantly augmented more than that of virus produced from control cells. The increase in infectivity occurred in proviral DNA synthesis. Further analysis revealed that Huwel interacted with HIV-1 Gag-Pol precursor protein through an IN domain. Our results suggest that Huwel in HIV-1 producer cells has a negative impact on early post-entry events during the next round of virus infection via association with an IN region of Gag-Pol.

• 出版日期2011-4