Identification of Interferon-Stimulated Gene 15 as an Antiviral Molecule during Sindbis Virus Infection In Vivo
Open Access
- 15 November 2005
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 79 (22), 13974-13983
- https://doi.org/10.1128/jvi.79.22.13974-13983.2005
Abstract
The innate immune response, and in particular the alpha/beta interferon (IFN-α/β) system, plays a critical role in the control of viral infections. Interferons α and β exert their antiviral effects through the induction of hundreds of interferon-induced (or -stimulated) genes (ISGs). While several of these ISGs have characterized antiviral functions, their actions alone do not explain all of the effects mediated by IFN-α/β. To identify additional IFN-induced antiviral molecules, we utilized a recombinant chimeric Sindbis virus to express selected ISGs in IFN-α/β receptor (IFN-α/βR)−/−mice and looked for attenuation of Sindbis virus infection. Using this approach, we identified a ubiquitin homolog, interferon-stimulated gene 15 (ISG15), as having antiviral activity. ISG15 expression protected against Sindbis virus-induced lethality and decreased Sindbis virus replication in multiple organs without inhibiting the spread of virus throughout the host. We establish that, much like ubiquitin, ISG15 requires its C-terminal LRLRGG motif to form intracellular conjugates. Finally, we demonstrate that ISG15's LRLRGG motif is also required for its antiviral activity. We conclude that ISG15 can be directly antiviral.Keywords
This publication has 51 references indexed in Scilit:
- Proteomic identification of proteins conjugated to ISG15 in mouse and human cellsBiochemical and Biophysical Research Communications, 2005
- A critical function for type I interferons in cancer immunoeditingNature Immunology, 2005
- SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral ReplicationJournal of Virology, 2004
- Critical Role of Complement and Viral Evasion of Complement in Acute, Persistent, and Latent γ-Herpesvirus InfectionImmunity, 2002
- Effects of PKR/RNase L-Dependent and Alternative Antiviral Pathways on Alphavirus Replication and PathogenesisViral Immunology, 2002
- Identification of Genes Involved in the Host Response to Neurovirulent Alphavirus InfectionJournal of Virology, 2001
- Distinct Functional Surface Regions on UbiquitinJournal of Biological Chemistry, 2001
- Interferons α and β as Immune Regulators—A New LookImmunity, 2001
- Conjugation of the 15-kDa Interferon-induced Ubiquitin Homolog Is Distinct from That of UbiquitinJournal of Biological Chemistry, 1996
- Functional Role of Type I and Type II Interferons in Antiviral DefenseScience, 1994