Open AccessIdentification of Interferon-Stimulated Gene 15 as an Antiviral Molecule during Sindbis Virus Infection In Vivo
Author(s) -
Deborah J. Lenschow,
Nadia V. Giannakopoulos,
Lacey J. Gunn,
Christine Johnston,
Andy K. O'Guin,
Robert E. Schmidt,
Beth Levine,
Herbert W. Virgin
Publication year - 2005
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.79.22.13974-13983.2005
Subject(s) - isg15 , sindbis virus , biology , interferon , virology , virus , interferon stimulated gene , alphavirus , viral replication , antiviral protein , innate immune system , gene , immune system , ubiquitin , immunology , genetics , rna
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.