The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins
Abstract
The host immune responses to infection lead to the production of type I interferon (IFN), and the upregulation of interferon-stimulated genes (ISGs) reduces virus replication and virus dissemination within a host. Ectopic expression of the interferon-induced 20-kDa exonuclease ISG20 suppressed replication of chikungunya virus and Venezuelan equine encephalitis virus, two mosquito-vectored RNA alphaviruses. Since the replication of alphavirus genomes occurs exclusively in the cytoplasm, the mechanism of nucleus-localized ISG20 inhibition of replication is unclear. In this study, we determined that ISG20 acts as a master regulator of over 100 genes, many of which are ISGs. Specifically, ISG20 upregulated IFIT1 genes and inhibited translation of the alphavirus genome. Furthermore, IFIT1-sensitive alphavirus replication was increased in Isg20 −/− mice compared to the replication of wild-type viruses but not in cells ectopically expressing ISG20. We propose that ISG20 acts as an indirect regulator of RNA virus replication in the cytoplasm through the upregulation of many other ISGs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 31, 2018
- Source ID
- 10.1128/msphere.00209-18
Entities
People
- Chengqun Sun
- Christopher M. Weiss
- Derek W Trobaugh
- Kate D. Ryman
- Michael S. Diamond
- Tiffany M. Lucas
- William B Klimstra
Organizations
- Defense Threat Reduction Agency
- National Institute of Allergy and Infectious Diseases
- University of Pittsburgh
- Washington University in St. Louis