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Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses.
J Immunol 2009; 183(11):6989-97JI

Abstract

Rhinovirus (RV), a ssRNA virus of the picornavirus family, is a major cause of the common cold as well as asthma and chronic obstructive pulmonary disease exacerbations. Viral dsRNA produced during replication may be recognized by the host pattern recognition receptors TLR-3, retinoic acid-inducible gene (RIG)-I, and melanoma differentiation-associated gene (MDA)-5. No study has yet identified the receptor required for sensing RV dsRNA. To examine this, BEAS-2B human bronchial epithelial cells were infected with intact RV-1B or replication-deficient UV-irradiated virus, and IFN and IFN-stimulated gene expression was determined by quantitative PCR. The separate requirements of RIG-I, MDA5, and IFN response factor (IRF)-3 were determined using their respective small interfering RNAs (siRNA). The requirement of TLR3 was determined using siRNA against the TLR3 adaptor molecule Toll/IL-1R homologous region-domain-containing adapter-inducing IFN-beta (TRIF). Intact RV-1B, but not UV-irradiated RV, induced IRF3 phosphorylation and dimerization, as well as mRNA expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, 10-kDa IFN-gamma-inducible protein/CXCL10, IL-8/CXCL8, and GM-CSF. siRNA against IRF3, MDA5, and TRIF, but not RIG-I, decreased RV-1B-induced expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, and inflammatory protein-10/CXCL10 but had no effect on IL-8/CXCL8 and GM-CSF. siRNAs against MDA5 and TRIF also reduced IRF3 dimerization. Finally, in primary cells, transfection with MDA5 siRNA significantly reduced IFN expression, as it did in BEAS-2B cells. These results suggest that TLR3 and MDA5, but not RIG-I, are required for maximal sensing of RV dsRNA and that TLR3 and MDA5 signal through a common downstream signaling intermediate, IRF3.

Authors+Show Affiliations

Department of Molecular and Integrative Physiology., University of Michigan, Ann Arbor, MI 48109, USANo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19890046

Citation

Wang, Qiong, et al. "Role of Double-stranded RNA Pattern Recognition Receptors in Rhinovirus-induced Airway Epithelial Cell Responses." Journal of Immunology (Baltimore, Md. : 1950), vol. 183, no. 11, 2009, pp. 6989-97.
Wang Q, Nagarkar DR, Bowman ER, et al. Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. J Immunol. 2009;183(11):6989-97.
Wang, Q., Nagarkar, D. R., Bowman, E. R., Schneider, D., Gosangi, B., Lei, J., ... Hershenson, M. B. (2009). Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. Journal of Immunology (Baltimore, Md. : 1950), 183(11), pp. 6989-97. doi:10.4049/jimmunol.0901386.
Wang Q, et al. Role of Double-stranded RNA Pattern Recognition Receptors in Rhinovirus-induced Airway Epithelial Cell Responses. J Immunol. 2009 Dec 1;183(11):6989-97. PubMed PMID: 19890046.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. AU - Wang,Qiong, AU - Nagarkar,Deepti R, AU - Bowman,Emily R, AU - Schneider,Dina, AU - Gosangi,Babina, AU - Lei,Jing, AU - Zhao,Ying, AU - McHenry,Christina L, AU - Burgens,Richai V, AU - Miller,David J, AU - Sajjan,Umadevi, AU - Hershenson,Marc B, Y1 - 2009/11/04/ PY - 2009/11/6/entrez PY - 2009/11/6/pubmed PY - 2009/12/23/medline SP - 6989 EP - 97 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 183 IS - 11 N2 - Rhinovirus (RV), a ssRNA virus of the picornavirus family, is a major cause of the common cold as well as asthma and chronic obstructive pulmonary disease exacerbations. Viral dsRNA produced during replication may be recognized by the host pattern recognition receptors TLR-3, retinoic acid-inducible gene (RIG)-I, and melanoma differentiation-associated gene (MDA)-5. No study has yet identified the receptor required for sensing RV dsRNA. To examine this, BEAS-2B human bronchial epithelial cells were infected with intact RV-1B or replication-deficient UV-irradiated virus, and IFN and IFN-stimulated gene expression was determined by quantitative PCR. The separate requirements of RIG-I, MDA5, and IFN response factor (IRF)-3 were determined using their respective small interfering RNAs (siRNA). The requirement of TLR3 was determined using siRNA against the TLR3 adaptor molecule Toll/IL-1R homologous region-domain-containing adapter-inducing IFN-beta (TRIF). Intact RV-1B, but not UV-irradiated RV, induced IRF3 phosphorylation and dimerization, as well as mRNA expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, 10-kDa IFN-gamma-inducible protein/CXCL10, IL-8/CXCL8, and GM-CSF. siRNA against IRF3, MDA5, and TRIF, but not RIG-I, decreased RV-1B-induced expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, and inflammatory protein-10/CXCL10 but had no effect on IL-8/CXCL8 and GM-CSF. siRNAs against MDA5 and TRIF also reduced IRF3 dimerization. Finally, in primary cells, transfection with MDA5 siRNA significantly reduced IFN expression, as it did in BEAS-2B cells. These results suggest that TLR3 and MDA5, but not RIG-I, are required for maximal sensing of RV dsRNA and that TLR3 and MDA5 signal through a common downstream signaling intermediate, IRF3. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/19890046/Role_of_double_stranded_RNA_pattern_recognition_receptors_in_rhinovirus_induced_airway_epithelial_cell_responses_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=19890046 DB - PRIME DP - Unbound Medicine ER -