SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses
Identifieur interne : 000006 ( Main/Exploration ); précédent : 000005; suivant : 000007SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses
Auteurs : Marco R. Straus [États-Unis] ; Jonathan T. Kinder [États-Unis] ; Michal Segall [États-Unis] ; Rebecca Ellis Dutch [États-Unis] ; Gary R. Whittaker [États-Unis]Source :
- Virology [ 0042-6822 ] ; 2020.
Abstract
Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 h post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.
Url:
DOI: 10.1016/j.virol.2020.01.004
PubMed: 32056846
PubMed Central: 7112099
Affiliations:
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Straus</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY</wicri:regionArea><placeName><region type="state">État de New York</region><settlement type="city">Ithaca (New York)</settlement></placeName><orgName type="university">Université Cornell</orgName></affiliation></author><author><name sortKey="Kinder, Jonathan T" sort="Kinder, Jonathan T" uniqKey="Kinder J" first="Jonathan T." last="Kinder">Jonathan T. Kinder</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY</wicri:regionArea><placeName><region type="state">Kentucky</region></placeName></affiliation></author><author><name sortKey="Segall, Michal" sort="Segall, Michal" uniqKey="Segall M" first="Michal" last="Segall">Michal Segall</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY</wicri:regionArea><placeName><region type="state">État de New York</region><settlement type="city">Ithaca (New York)</settlement></placeName><orgName type="university">Université Cornell</orgName></affiliation></author><author><name sortKey="Dutch, Rebecca Ellis" sort="Dutch, Rebecca Ellis" uniqKey="Dutch R" first="Rebecca Ellis" last="Dutch">Rebecca Ellis Dutch</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY</wicri:regionArea><placeName><region type="state">Kentucky</region></placeName></affiliation></author><author><name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R." last="Whittaker">Gary R. Whittaker</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY</wicri:regionArea><placeName><region type="state">État de New York</region><settlement type="city">Ithaca (New York)</settlement></placeName><orgName type="university">Université Cornell</orgName></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 h post-infection. 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Simmons</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Kentucky</li><li>État de New York</li></region><settlement><li>Ithaca (New York)</li></settlement><orgName><li>Université Cornell</li></orgName></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Straus, Marco R" sort="Straus, Marco R" uniqKey="Straus M" first="Marco R." last="Straus">Marco R. Straus</name></region><name sortKey="Dutch, Rebecca Ellis" sort="Dutch, Rebecca Ellis" uniqKey="Dutch R" first="Rebecca Ellis" last="Dutch">Rebecca Ellis Dutch</name><name sortKey="Kinder, Jonathan T" sort="Kinder, Jonathan T" uniqKey="Kinder J" first="Jonathan T." last="Kinder">Jonathan T. Kinder</name><name sortKey="Segall, Michal" sort="Segall, Michal" uniqKey="Segall M" first="Michal" last="Segall">Michal Segall</name><name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R." last="Whittaker">Gary R. Whittaker</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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