Role of retinoic acid inducible gene-I in human metapneumovirus-induced cellular signalling

S. Liao, Xiaoyong Bao, T. Liu, S. Lai, K. Li, Roberto Garofalo, Antonella Casola

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Human metapneumovirus (HMPV) is a recently discovered pathogen that causes a significant proportion of respiratory infections in young infants, the elderly and immunocompromised patients. Very little is known regarding the cellular signalling elicited by this virus in airway epithelial cells, the target of HMPV infection. In this study, we investigated the role of the RNA helicases retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene-5 (MDA-5) as the main pattern recognition receptors (PRRs) involved in viral detection and subsequent expression of proinflammatory and antiviral genes. HMPV infection readily induced RIG-I and MDA-5 gene and protein expression in A549 cells, a type II-like alveolar epithelial cell line. Expression of dominant-negative (DN) RIG-I or downregulation of RIG-I gene expression using small interfering RNA (siRNA) significantly decreased HMPV-induced beta interferon (IFN-β), interleukin (IL)-8 and RANTES gene transcription, by inhibiting viral-induced activation of nuclear factor (NF)-κB and interferon regulatory factor (IRF), leading to enhanced viral replication. On the other hand, MDA-5 did not seem to play a significant role in HMPV-induced cellular responses. Mitochondrial antiviral signalling protein (MAVS), an adaptor protein linking both RIG-1 and MDA-5 to downstream activation of IRF-3 and NF-κB, was also necessary for HMPV-induced cellular signalling. Expression of a DN MAVS significantly reduced IFN-β and chemokine gene transcription, by inhibiting NF-κB- and IRF-dependent gene transcription, in response to HMPV infection. Our results show that HMPV activates the RIG-I-MAVS signalling pathway in airway epithelial cells, leading to the expression of important proinflammatory and antiviral molecules involved in the innate immune response to viruses.

Original languageEnglish (US)
Pages (from-to)1978-1986
Number of pages9
JournalJournal of General Virology
Volume89
Issue number8
DOIs
StatePublished - Aug 2008

Fingerprint

Metapneumovirus
Tretinoin
Genes
Antiviral Agents
Melanoma
Interferon Regulatory Factors
Proteins
Infection
Epithelial Cells
Interferon Regulatory Factor-3
RNA Helicases
Viruses
Alveolar Epithelial Cells
Pattern Recognition Receptors
Gene Expression
Virus Activation
Chemokine CCL5
Mitochondrial Genes
Interferon-beta
Immunocompromised Host

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Role of retinoic acid inducible gene-I in human metapneumovirus-induced cellular signalling. / Liao, S.; Bao, Xiaoyong; Liu, T.; Lai, S.; Li, K.; Garofalo, Roberto; Casola, Antonella.

In: Journal of General Virology, Vol. 89, No. 8, 08.2008, p. 1978-1986.

Research output: Contribution to journalArticle

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