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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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| Published in: | Infection, genetics and evolution genetics and evolution, 2021-12, Vol.96, p.105096-105096, Article 105096 |
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| container_title | Infection, genetics and evolution |
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| creator | Bitko, Vira Barik, Sailen |
| description | 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.
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•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. |
| doi_str_mv | 10.1016/j.meegid.2021.105096 |
| format | article |
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[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.</description><identifier>ISSN: 1567-1348</identifier><identifier>EISSN: 1567-7257</identifier><identifier>DOI: 10.1016/j.meegid.2021.105096</identifier><identifier>PMID: 34601094</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>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</subject><ispartof>Infection, genetics and evolution, 2021-12, Vol.96, p.105096-105096, Article 105096</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c311t-63e82f52dd7edddc223ec6bd0fd161e66c2660f31fd91e3c1a91d0f9f2139b2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34601094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bitko, Vira</creatorcontrib><creatorcontrib>Barik, Sailen</creatorcontrib><title>Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response</title><title>Infection, genetics and evolution</title><addtitle>Infect Genet Evol</addtitle><description>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.</description><subject>A549 Cells</subject><subject>Ectodomain</subject><subject>Glycoproteins</subject><subject>Glycoproteins - metabolism</subject><subject>HMPV</subject><subject>Humans</subject><subject>IFN regulatory factor</subject><subject>Immunity, Innate</subject><subject>Interferon</subject><subject>Metapneumovirus</subject><subject>Metapneumovirus - physiology</subject><subject>Paramyxoviridae Infections - immunology</subject><subject>Paramyxoviridae Infections - virology</subject><subject>STAT</subject><subject>Viral Proteins - metabolism</subject><issn>1567-1348</issn><issn>1567-7257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQQIMotlb_gUiOXlozSZvtXgQpfkFBEL0JYZvMtim7SU12C_33Ztnq0dNkMm8yk0fINbAJMJB320mNuLZmwhmHdDVjuTwhQ5jJbJzxWXZ6PIOYzgfkIsYtY5AxPj8nAzGVDFg-HZKvd18h9SWtsSl2Dtva720oKrquDtrvgm_Qukito80GKe6LaL3r-C7d-NhQjVWV6q5okNq6bh3SgHHnXcRLclYWVcSrYxyRz6fHj8XLePn2_Lp4WI61AGjGUuCclzNuTIbGGM25QC1XhpUGJKCUmkvJSgGlyQGFhiKHVMxLDiJf8ZUYkdv-3bTvd4uxUbWN3V6FQ99GlWzkbC45zxI67VEdfIwBS7ULti7CQQFTnVe1Vb1X1XlVvdfUdnOc0K5qNH9NvyITcN8DmP65txhU1BadRmMD6kYZb_-f8APs14xd</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Bitko, Vira</creator><creator>Barik, Sailen</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202112</creationdate><title>Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response</title><author>Bitko, Vira ; Barik, Sailen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-63e82f52dd7edddc223ec6bd0fd161e66c2660f31fd91e3c1a91d0f9f2139b2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>A549 Cells</topic><topic>Ectodomain</topic><topic>Glycoproteins</topic><topic>Glycoproteins - metabolism</topic><topic>HMPV</topic><topic>Humans</topic><topic>IFN regulatory factor</topic><topic>Immunity, Innate</topic><topic>Interferon</topic><topic>Metapneumovirus</topic><topic>Metapneumovirus - physiology</topic><topic>Paramyxoviridae Infections - immunology</topic><topic>Paramyxoviridae Infections - virology</topic><topic>STAT</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bitko, Vira</creatorcontrib><creatorcontrib>Barik, Sailen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Infection, genetics and evolution</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bitko, Vira</au><au>Barik, Sailen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response</atitle><jtitle>Infection, genetics and evolution</jtitle><addtitle>Infect Genet Evol</addtitle><date>2021-12</date><risdate>2021</risdate><volume>96</volume><spage>105096</spage><epage>105096</epage><pages>105096-105096</pages><artnum>105096</artnum><issn>1567-1348</issn><eissn>1567-7257</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34601094</pmid><doi>10.1016/j.meegid.2021.105096</doi><tpages>1</tpages></addata></record> |
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| source | ScienceDirect Journals |
| 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 |
| title | Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response |
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