Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium.

Abstract:

:The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Slater L,Bartlett NW,Haas JJ,Zhu J,Message SD,Walton RP,Sykes A,Dahdaleh S,Clarke DL,Belvisi MG,Kon OM,Fujita T,Jeffery PK,Johnston SL,Edwards MR

doi

10.1371/journal.ppat.1001178

subject

Has Abstract

pub_date

2010-11-04 00:00:00

pages

e1001178

issue

11

eissn

1553-7366

issn

1553-7374

journal_volume

6

pub_type

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