Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15.
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.
Mesh Terms:
Antiviral Agents, Blotting, Western, Cell Line, Cytokines, DNA, Complementary, DNA-Binding Proteins, Dose-Response Relationship, Drug, Endosomal Sorting Complexes Required for Transport, Endosomes, Gene Products, gag, Genetic Vectors, HIV-1, Humans, Immunoprecipitation, Lentivirus, Models, Statistical, Plasmids, RNA, Small Interfering, Time Factors, Transcription Factors, Transfection, Ubiquitin, Ubiquitins, Virus Replication
Antiviral Agents, Blotting, Western, Cell Line, Cytokines, DNA, Complementary, DNA-Binding Proteins, Dose-Response Relationship, Drug, Endosomal Sorting Complexes Required for Transport, Endosomes, Gene Products, gag, Genetic Vectors, HIV-1, Humans, Immunoprecipitation, Lentivirus, Models, Statistical, Plasmids, RNA, Small Interfering, Time Factors, Transcription Factors, Transfection, Ubiquitin, Ubiquitins, Virus Replication
Proc. Natl. Acad. Sci. U.S.A.
Date: Jan. 31, 2006
PubMed ID: 16434471
View in: Pubmed Google Scholar
Download Curated Data For This Publication
102013
Switch View:
- Interactions 2
- PTM Genes 2