Human metapneumovirus glycoprotein G is an important virulence factor

Human metapneumovirus Human metapneumovirus (hMPV), a member of the Paramyxoviridae family, is an important cause of respiratory morbidity throughout life. The contribution of viral-specific proteins to the pathogenesis of hMPV infection and immune evasion is largely unknown. Previous work has suggested that the glycoprotein G of hMPV is not necessary for the process of viral fusion and attachment to host cells, and a recombinant hMPV lacking the G protein shows an attenuated phenotype in the respiratory tract of animal models of infection. Airway epithelial cells, a major component of the innate immune system, are a primary target of hMPV infection. A recent study shows that hMPV G protein functions as a major inhibitory factor of the host antiviral response by blocking production of inducible chemokines and IFN-α/β. A major finding of this work is the demonstration that hMPV G protein interacts with RIG-I, a cytoplasmic viral sensor. As result, hMPV G protein inhibits RIG-I-dependent signaling pathways, including activation of NF-κB and IRF-3, two transcription factors necessary for the synthesis of inflammatory and antiviral cytokines. Understanding the function of hMPV proteins is critical for the future design of effective antiviral therapies and rationale design of vaccine candidates.

Human Metapneumovirus Glycoprotein G Inhibits Innate Immune Responses. PLoS Pathog 2008 4(5): e1000077
Human metapneumovirus (hMPV), a member of the Paramyxoviridae family, is an important cause of respiratory morbidity throughout life. The contribution of viral-specific proteins to the pathogenesis of hMPV infection and immune evasion is largely unknown. Previous work has suggested that the glycoprotein G of hMPV is not necessary for the process of viral fusion and attachment to host cells, and a recombinant hMPV lacking the G protein (rhMPV-ΔG) shows an attenuated phenotype in the respiratory tract of animal models of infection. Airway epithelial cells, a major component of the innate immune system, are a primary target of hMPV infection. In this study, we show that hMPV G protein functions as a major inhibitory factor of the host antiviral response by blocking production of inducible chemokines and IFN-α/β. A major finding of this work is the demonstration that hMPV G protein interacts with RIG-I, a cytoplasmic viral sensor. As result, hMPV G protein inhibits RIG-I-dependent signaling pathways, including activation of NF-κB and IRF-3, two transcription factors necessary for the synthesis of inflammatory and antiviral cytokines. Understanding the function of hMPV proteins is critical for the future design of effective antiviral therapies and rationale design of vaccine candidates.

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