Human metapneumovirus glycoprotein G inhibits innate immune responses

Xiaoyong Bao, Tianshuang Liu, Yichu Shan, Kui Li, Roberto Garofalo, Antonella Casola

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infection in infants, as well as in the elderly and immunocompromised patients. No effective treatment or vaccine for hMPV is currently available. A recombinant hMPV lacking the G protein (rhMPV-ΔG) was recently developed as a potential vaccine candidate and shown to be attenuated in the respiratory tract of a rodent model of infection. The mechanism of its attenuation, as well as the role of G protein in modulation of hMPV-induced cellular responses in vitro, as well as in vivo, is currently unknown. In this study, we found that rhMPV-ΔG-infected airway epithelial cells produced higher levels of chemokines and type I interferon (IFN) compared to cells infected with rhMPV-WT. Infection of airway epithelial cells with rhMPV-ΔG enhanced activation of transcription factors belonging to the nuclear factor (NF)-κB and interferon regulatory factor (IRF) families, as revealed by increased nuclear translocation and/or phosphorylation of these transcription factors. Compared to rhMPV-WT, rhMPV-ΔG also increased IRF and NF-κB-dependent gene transcription, which was reversely inhibited by G protein expression. Since RNA helicases have been shown to play a fundamental role in initiating viral-induced cellular signaling, we investigated whether retinoic induced gene (RIG)-I was the target of G protein inhibitory activity. We found that indeed G protein associated with RIG-I and inhibited RIG-I-dependent gene transcription, identifying an important mechanism by which hMPV affects innate immune responses. This is the first study investigating the role of hMPV G protein in cellular signaling and identifies G as an important virulence factor, as it inhibits the production of important immune and antiviral mediators by targeting RIG-I, a major intracellular viral RNA sensor.

Original languageEnglish (US)
Article numbere1000077
JournalPLoS Pathogens
Volume4
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

GTP-Binding Proteins
Innate Immunity
Metapneumovirus
Interferon Regulatory Factors
Genes
Transcription Factors
Vaccines
Epithelial Cells
RNA Helicases
human metapneumovirus G glycoprotein
Interferon Type I
Viral RNA
Immunocompromised Host
Virulence Factors
Infection
Chemokines
Respiratory Tract Infections
Respiratory System
Antiviral Agents
Rodentia

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Human metapneumovirus glycoprotein G inhibits innate immune responses. / Bao, Xiaoyong; Liu, Tianshuang; Shan, Yichu; Li, Kui; Garofalo, Roberto; Casola, Antonella.

In: PLoS Pathogens, Vol. 4, No. 5, e1000077, 05.2008.

Research output: Contribution to journalArticle

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