Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: 336-346

Zeitschrift: Cell Host & Microbe

Bandnummer: 13

Heftnummer: 3

ISSN: 1931-3128

eISSN: 1934-6069

DOI Link: https://doi.org/10.1016/j.chom.2013.01.012

Verlag: Cell Press

Abstract: 

Host defense to RNA viruses depends on rapid intracellular recognition of viral RNA by two cytoplasmic RNA helicases: RIG-I and MDA5. RNA transfection experiments indicate that RIG-I responds to naked double-stranded RNAs (dsRNAs) with a triphosphorylated 5′ (5′ppp) terminus. However, the identity of the RIG-I stimulating viral structures in an authentic infection context remains unresolved. We show that incoming viral nucleocapsids containing a 5′ppp dsRNA “panhandle” structure trigger antiviral signaling that commences with RIG-I, is mediated through the adaptor protein MAVS, and terminates with transcription factor IRF-3. Independent of mammalian cofactors or viral polymerase activity, RIG-I bound to viral nucleocapsids, underwent a conformational switch, and homo-oligomerized. Enzymatic probing and superresolution microscopy suggest that RIG-I interacts with the panhandle structure of the viral nucleocapsids. These results define cytoplasmic entry of nucleocapsids as the proximal RIG-I-sensitive step during infection and establish viral nucleocapsids with a 5′ppp dsRNA panhandle as a RIG-I activator.

Harvard-Zitierstil: Weber, M., Gawanbacht, A., Habjan, M., Rang, A., Borner, C., Schmidt, A., et al. (2013) Incoming RNA Virus Nucleocapsids Containing a 5′-Triphosphorylated Genome Activate RIG-I and Antiviral Signaling, Cell Host & Microbe, 13(3), pp. 336-346. https://doi.org/10.1016/j.chom.2013.01.012

APA-Zitierstil: Weber, M., Gawanbacht, A., Habjan, M., Rang, A., Borner, C., Schmidt, A., Veitinger, S., Jacob, R., Devignot, S., Kochs, G., García-Sastre, A., & Weber, F. (2013). Incoming RNA Virus Nucleocapsids Containing a 5′-Triphosphorylated Genome Activate RIG-I and Antiviral Signaling. Cell Host & Microbe. 13(3), 336-346. https://doi.org/10.1016/j.chom.2013.01.012