Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response

Human metapneumovirus (HMPV), an unsegmented negative-strand RNA virus, is the second most detected respiratory pathogen and one of the leading causes of respiratory illness in infants and immunodeficient individuals. HMPV infection of permissive cells in culture triggers a transient IFN response, w...

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Bibliographic Details
Published in:Infection, genetics and evolution genetics and evolution, 2021-12, Vol.96, p.105096-105096, Article 105096
Main Authors: Bitko, Vira, Barik, Sailen
Format: Article
Language:English
Subjects:
A549 Cells
Ectodomain
Glycoproteins
Glycoproteins - metabolism
HMPV
Humans
IFN regulatory factor
Immunity, Innate
Interferon
Metapneumovirus
Metapneumovirus - physiology
Paramyxoviridae Infections - immunology
Paramyxoviridae Infections - virology
STAT
Viral Proteins - metabolism
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Summary:Human metapneumovirus (HMPV), an unsegmented negative-strand RNA virus, is the second most detected respiratory pathogen and one of the leading causes of respiratory illness in infants and immunodeficient individuals. HMPV infection of permissive cells in culture triggers a transient IFN response, which is efficiently suppressed later in infection. We report that two structural glycoproteins of the virus – namely G (Glycoprotein) and SH (Small Hydrophobic) – suppress the type I interferon (IFN) response in cell culture. This is manifested by inhibition of diverse steps of IFN induction and response, such as phosphorylation and nuclear translocation of IFN regulatory factor-3 and -7 (IRF3, IRF7), major transcription factors of the IFN gene. Furthermore, HMPV suppresses the cellular response to IFN by inhibiting the phosphorylation of STAT1 (Signal Transducer and Activator of Transcription 1), required for the induction of IFN-stimulated genes that act as antivirals. Site-directed mutagenesis revealed an important role of critical cysteine (Cys) residues in the Cys-rich carboxy terminal region of the SH protein in IFN suppression, whereas for G, the ectodomain plays a role. These results shed light on the mechanism of IFN suppression by HMPV, and may also offer avenues for new antiviral approaches in the future. [Display omitted] •Human metapneumovirus (HMPV) is a major respiratory pathogen in children.•The G (Glycoprotein) and SH (Small Hydrophobic) proteins of HMPV suppress IFN.•Both G and SH are structural glycoproteins, localized in the membrane.•Both proteins suppress multiple steps of the IFN induction and response pathways.•The ectodomain of G and specific Cys residues of SH are important for IFN suppression.
ISSN:1567-1348
1567-7257
DOI:10.1016/j.meegid.2021.105096