Human metapneumovirus glycoprotein G inhibits innate immune responses.

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-Delta G) was recently develope...

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Autores principales:	Xiaoyong Bao, Tianshuang Liu, Yichu Shan, Kui Li, Roberto P Garofalo, Antonella Casola
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f98b93caaf6e47e696644f704011b2e2
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spelling	oai:doaj.org-article:f98b93caaf6e47e696644f704011b2e22021-11-25T05:46:33ZHuman metapneumovirus glycoprotein G inhibits innate immune responses.1553-73661553-737410.1371/journal.ppat.1000077https://doaj.org/article/f98b93caaf6e47e696644f704011b2e22008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18516301/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human 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-Delta G) 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-Delta G-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-Delta G enhanced activation of transcription factors belonging to the nuclear factor (NF)-kappaB and interferon regulatory factor (IRF) families, as revealed by increased nuclear translocation and/or phosphorylation of these transcription factors. Compared to rhMPV-WT, rhMPV-Delta G also increased IRF- and NF-kappaB-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.Xiaoyong BaoTianshuang LiuYichu ShanKui LiRoberto P GarofaloAntonella CasolaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 5, p e1000077 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Xiaoyong Bao Tianshuang Liu Yichu Shan Kui Li Roberto P Garofalo Antonella Casola Human metapneumovirus glycoprotein G inhibits innate immune responses.
description	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-Delta G) 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-Delta G-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-Delta G enhanced activation of transcription factors belonging to the nuclear factor (NF)-kappaB and interferon regulatory factor (IRF) families, as revealed by increased nuclear translocation and/or phosphorylation of these transcription factors. Compared to rhMPV-WT, rhMPV-Delta G also increased IRF- and NF-kappaB-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.
format	article
author	Xiaoyong Bao Tianshuang Liu Yichu Shan Kui Li Roberto P Garofalo Antonella Casola
author_facet	Xiaoyong Bao Tianshuang Liu Yichu Shan Kui Li Roberto P Garofalo Antonella Casola
author_sort	Xiaoyong Bao
title	Human metapneumovirus glycoprotein G inhibits innate immune responses.
title_short	Human metapneumovirus glycoprotein G inhibits innate immune responses.
title_full	Human metapneumovirus glycoprotein G inhibits innate immune responses.
title_fullStr	Human metapneumovirus glycoprotein G inhibits innate immune responses.
title_full_unstemmed	Human metapneumovirus glycoprotein G inhibits innate immune responses.
title_sort	human metapneumovirus glycoprotein g inhibits innate immune responses.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/f98b93caaf6e47e696644f704011b2e2
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_version_	1718414495833915392

Human metapneumovirus glycoprotein G inhibits innate immune responses.

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