Incoming RNA virus nucleocapsids containing a 5'-triphosphorylated genome activate RIG-I and antiviral signaling.
Cell Host Microbe
; 13(3): 336-46, 2013 Mar 13.
Article
in En
| MEDLINE
| ID: mdl-23498958
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Virus Infections
/
RNA Viruses
/
Nucleocapsid
/
DEAD-box RNA Helicases
Limits:
Humans
Language:
En
Journal:
Cell Host Microbe
Journal subject:
MICROBIOLOGIA
Year:
2013
Document type:
Article
Affiliation country: