Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity

Yueh Ming Loo, Jamie Fornek, Nanette Crochet, Gagan Bajwa, Olivia Perwitasari, Luis Martinez-Sobrido, Shizuo Akira, Michelle A. Gill, Adolfo García-Sastre, Michael G. Katze, Michael Gale

Research output: Contribution to journalArticle

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Abstract

Alpha/beta interferon immune defenses are essential for resistance to viruses and can be triggered through the actions of the cytoplasmic helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Signaling by each is initiated by the recognition of viral products such as RNA and occurs through downstream interaction with the IPS-1 adaptor protein. We directly compared the innate immune signaling requirements of representative viruses of the Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Reoviridae for RIG-I, MDA5, and interferon promoter-stimulating factor 1 (IPS-1). In cultured fibroblasts, IPS-1 was essential for innate immune signaling of downstream interferon regulatory factor 3 activation and interferon-stimulated gene expression, but the requirements for RIG-I and MDA5 were variable. Each was individually dispensable for signaling triggered by reovirus and dengue virus, whereas RIG-I was essential for signaling by influenza A virus, influenza B virus, and human respiratory syncytial virus. Functional genomics analyses identified cellular genes triggered during influenza A virus infection whose expression was strictly dependent on RIG-I and which are involved in processes of innate or adaptive immunity, apoptosis, cytokine signaling, and inflammation associated with the host response to contemporary and pandemic strains of influenza virus. These results define IPS-1-dependent signaling as an essential feature of host immunity to RNA virus infection. Our observations further demonstrate differential and redundant roles for RIG-I and MDA5 in pathogen recognition and innate immune signaling that may reflect unique and shared biologic properties of RNA viruses whose differential triggering and control of gene expression may impact pathogenesis and infection.

Original languageEnglish (US)
Pages (from-to)335-345
Number of pages11
JournalJournal of Virology
Volume82
Issue number1
DOIs
StatePublished - Jan 2008

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RNA Viruses
retinoic acid
melanoma
Tretinoin
Innate Immunity
Melanoma
interferons
Genes
genes
Interferons
promoter regions
Reoviridae
Interferon-beta
Influenza A virus
Orthomyxoviridae
RNA Virus Infections
RNA viruses
innate immunity
Paramyxoviridae
Human respiratory syncytial virus

ASJC Scopus subject areas

  • Immunology

Cite this

Loo, Y. M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., ... Gale, M. (2008). Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. Journal of Virology, 82(1), 335-345. https://doi.org/10.1128/JVI.01080-07

Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. / Loo, Yueh Ming; Fornek, Jamie; Crochet, Nanette; Bajwa, Gagan; Perwitasari, Olivia; Martinez-Sobrido, Luis; Akira, Shizuo; Gill, Michelle A.; García-Sastre, Adolfo; Katze, Michael G.; Gale, Michael.

In: Journal of Virology, Vol. 82, No. 1, 01.2008, p. 335-345.

Research output: Contribution to journalArticle

Loo, YM, Fornek, J, Crochet, N, Bajwa, G, Perwitasari, O, Martinez-Sobrido, L, Akira, S, Gill, MA, García-Sastre, A, Katze, MG & Gale, M 2008, 'Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity', Journal of Virology, vol. 82, no. 1, pp. 335-345. https://doi.org/10.1128/JVI.01080-07
Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. Journal of Virology. 2008 Jan;82(1):335-345. https://doi.org/10.1128/JVI.01080-07
Loo, Yueh Ming ; Fornek, Jamie ; Crochet, Nanette ; Bajwa, Gagan ; Perwitasari, Olivia ; Martinez-Sobrido, Luis ; Akira, Shizuo ; Gill, Michelle A. ; García-Sastre, Adolfo ; Katze, Michael G. ; Gale, Michael. / Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. In: Journal of Virology. 2008 ; Vol. 82, No. 1. pp. 335-345.
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