Document Type
Article
Publication Date
2006
Publication Title
Proceedings of the National Academy of Sciences of the United States of America
Department
Geisel School of Medicine
Abstract
The goal of this study was to elucidate the molecular mechanism by which type I IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits release of HIV-1 virions without having any effect on the synthesis of HIV-1 proteins in the cells. ISG15 expression specifically inhibited ubiquitination of Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag-Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells. Elimination of ISG15 expression by small interfering RNA reversed the IFN-mediated inhibition of HIV-1 replication and release of virions. These results indicated a critical role for ISG15 in the IFN-mediated inhibition of late stages of HIV-1 assembly and release and pointed to a mechanism by which the innate antiviral response targets the cellular endosomal trafficking pathway used by HIV-1 to exit the cell. Identification of ISG15 as the critical component in IFN-mediated inhibition of HIV-1 release advances the understanding of the IFN-mediated inhibition of HIV-1 replication and uncovers a target for the anti HIV-1 therapy.
DOI
10.1073/pnas.0510518103
Dartmouth Digital Commons Citation
Okumura, Atsushi; Lu, Gengshi; Pitha-Rowe, Ian; and Pitha, Paula M., "Innate Antiviral Response Targets HIV-1 Release by the Induction of Ubiquitin-Like Protein ISG15" (2006). Dartmouth Scholarship. 1393.
https://digitalcommons.dartmouth.edu/facoa/1393
