RGD Reference Report - Mouse STAT2 restricts early dengue virus replication. - Rat Genome Database

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Mouse STAT2 restricts early dengue virus replication.

Authors: Ashour, Joseph  Morrison, Juliet  Laurent-Rolle, Maudry  Belicha-Villanueva, Alan  Plumlee, Courtney Ray  Bernal-Rubio, Dabeiba  Williams, Katherine L  Harris, Eva  Fernandez-Sesma, Ana  Schindler, Christian  García-Sastre, Adolfo 
Citation: Ashour J, etal., Cell Host Microbe. 2010 Nov 18;8(5):410-21. doi: 10.1016/j.chom.2010.10.007.
RGD ID: 41789625
Pubmed: (View Article at PubMed) PMID:21075352
DOI: Full-text: DOI:10.1016/j.chom.2010.10.007

Dengue virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type I interferon signaling pathway, and targets it for degradation. We now demonstrate that the ability of dengue NS5 to associate with and degrade STAT2 is species specific. Thus, NS5 is able to bind and degrade human STAT2, but not mouse STAT2. This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5-mediated IFN antagonism is essential for efficient virus replication. Moreover, we demonstrate that differences in NS5 mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2(-/-) mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. These results suggest that overcoming this restriction through transgenic mouse technology may help in the development of a long-sought immune-competent mouse model of dengue virus infection.

Annotation

Disease Annotations    
dengue disease  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Mus musculus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Homo sapiens)
STAT2  (signal transducer and activator of transcription 2)


Additional Information