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An attenuating mutation in a neurovirulent Sindbis virus strain interacts with the IPS-1 signaling pathway in vivo
- Source :
- Virology. 435:269-280
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The AR86 strain of Sindbis virus causes lethal neurologic disease in adult mice. Previous studies have identified a virulence determinant at nonstructural protein (nsP) 1 position 538 that regulates neurovirulence, modulates clearance from the CNS, and interferes with the type I interferon pathway. The studies herein demonstrate that in the absence of type I interferon signaling, the attenuated mutant exhibited equivalent virulence to S300 virus. Furthermore, both S300 and nsP1 T538I viruses displayed similar neurovirulence and replication kinetics in IPS-1−/− mice. TRIF dependent signaling played a modest role in protecting against disease by both S300 and nsP1 T538I, but did not contribute to control of nsP1 T538I replication within the CNS, while MyD88 played no role in the disease process. These results indicate that the control of the nsP1 T538I mutant virus is largely mediated by IPS-1-dependent RLR signaling, with TRIF-dependent TLR signaling also contributing to protection from virus-induced neurologic disease.
- Subjects :
- Pattern recognition receptors
Sindbis virus
Neurovirulence
viruses
Virulence
Alphavirus
Viral Nonstructural Proteins
Biology
Virus Replication
Article
Virus
Cell Line
Mice
03 medical and health sciences
Interferon
Virology
Sindbis
medicine
Animals
Adaptor Proteins, Signal Transducing
IPS-1
030304 developmental biology
0303 health sciences
Alphavirus Infections
030302 biochemistry & molecular biology
biology.organism_classification
3. Good health
Mice, Inbred C57BL
Adaptor Proteins, Vesicular Transport
Gene Expression Regulation
Viral replication
TRIF
Interferon Type I
Mutation
Myeloid Differentiation Factor 88
Central Nervous System Viral Diseases
Female
Sindbis Virus
Interferon type I
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00426822
- Volume :
- 435
- Database :
- OpenAIRE
- Journal :
- Virology
- Accession number :
- edsair.doi.dedup.....74f8967871aaaa0cd7f17079254c0db8