The Hemagglutinin Cleavability of a Virulent Avian Influenza Virus by Subtilisin-like Endoproteases Is Influenced by the Amino Acid Immediately Downstream of the Cleavage Site
Many viral membrane glycoproteins are post-translationally processed by intracellular endoproteases such as subtilisin-like proteases. These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 1995-07, Vol.210 (2), p.466-470 |
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| creator | Horimoto, Taisuke Kawaoka, Yoshihiro |
| description | Many viral membrane glycoproteins are post-translationally processed by intracellular endoproteases such as subtilisin-like proteases. These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the glycine residue immediately downstream of the cleavage site (P1) of hemagglutinin (HA) from a virulent avian influenza virus, A/turkey/Ontario/7732/66 (H5N9) (R-R-R-K-K-R/G), to examine the effect of this mutation on its clevability. Substitution of Gly with Ile, Leu, Val, or Pro, but not Ala, Asp, Phe, His, Ser, or Thr, resulted in substantial reduction of HA cleavage by endogenous endoproteases in CV-1 cells and by vaccinia-expressed PC6 and, albeit to a lesser extent, furin. We conclude that HA cleavage by subtilisin-like proteases is influenced by the downstream P1 amino acid in the absence of upstream cleavage site sequence alterations. |
| doi_str_mv | 10.1006/viro.1995.1363 |
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These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the glycine residue immediately downstream of the cleavage site (P1) of hemagglutinin (HA) from a virulent avian influenza virus, A/turkey/Ontario/7732/66 (H5N9) (R-R-R-K-K-R/G), to examine the effect of this mutation on its clevability. Substitution of Gly with Ile, Leu, Val, or Pro, but not Ala, Asp, Phe, His, Ser, or Thr, resulted in substantial reduction of HA cleavage by endogenous endoproteases in CV-1 cells and by vaccinia-expressed PC6 and, albeit to a lesser extent, furin. We conclude that HA cleavage by subtilisin-like proteases is influenced by the downstream P1 amino acid in the absence of upstream cleavage site sequence alterations.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1006/viro.1995.1363</identifier><identifier>PMID: 7618281</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AGGLUTININE ; AGLUTININAS ; Amino Acid Sequence ; Amino Acids - physiology ; COMPOSICION QUIMICA ; COMPOSITION CHIMIQUE ; Furin ; glycine ; Hemagglutinins, Viral - genetics ; Hemagglutinins, Viral - metabolism ; Influenza A virus - enzymology ; Influenza A virus - genetics ; Influenza A virus - metabolism ; INFLUENZAVIRUS AVIAIRE ; Molecular Sequence Data ; MUTACION ; MUTATION ; Mutation - physiology ; PODER PATOGENO ; POUVOIR PATHOGENE ; Proprotein Convertase 5 ; PROTEASAS ; PROTEASE ; Protein Processing, Post-Translational - genetics ; PROTEOLISIS ; PROTEOLYSE ; Serine Endopeptidases - metabolism ; Substrate Specificity ; Subtilisins - metabolism ; Tumor Cells, Cultured ; Vaccinia virus - genetics ; VIRUS DE LA INFLUENZA AVIAR</subject><ispartof>Virology (New York, N.Y.), 1995-07, Vol.210 (2), p.466-470</ispartof><rights>1995 Academic Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-446857e8098c248dde83ce12a62446b4a9dbfc7e3b33db215a09ba917b59279f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/viro.1995.1363$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7618281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horimoto, Taisuke</creatorcontrib><creatorcontrib>Kawaoka, Yoshihiro</creatorcontrib><title>The Hemagglutinin Cleavability of a Virulent Avian Influenza Virus by Subtilisin-like Endoproteases Is Influenced by the Amino Acid Immediately Downstream of the Cleavage Site</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>Many viral membrane glycoproteins are post-translationally processed by intracellular endoproteases such as subtilisin-like proteases. These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the glycine residue immediately downstream of the cleavage site (P1) of hemagglutinin (HA) from a virulent avian influenza virus, A/turkey/Ontario/7732/66 (H5N9) (R-R-R-K-K-R/G), to examine the effect of this mutation on its clevability. Substitution of Gly with Ile, Leu, Val, or Pro, but not Ala, Asp, Phe, His, Ser, or Thr, resulted in substantial reduction of HA cleavage by endogenous endoproteases in CV-1 cells and by vaccinia-expressed PC6 and, albeit to a lesser extent, furin. We conclude that HA cleavage by subtilisin-like proteases is influenced by the downstream P1 amino acid in the absence of upstream cleavage site sequence alterations.</description><subject>AGGLUTININE</subject><subject>AGLUTININAS</subject><subject>Amino Acid Sequence</subject><subject>Amino Acids - physiology</subject><subject>COMPOSICION QUIMICA</subject><subject>COMPOSITION CHIMIQUE</subject><subject>Furin</subject><subject>glycine</subject><subject>Hemagglutinins, Viral - genetics</subject><subject>Hemagglutinins, Viral - metabolism</subject><subject>Influenza A virus - enzymology</subject><subject>Influenza A virus - genetics</subject><subject>Influenza A virus - metabolism</subject><subject>INFLUENZAVIRUS AVIAIRE</subject><subject>Molecular Sequence Data</subject><subject>MUTACION</subject><subject>MUTATION</subject><subject>Mutation - physiology</subject><subject>PODER PATOGENO</subject><subject>POUVOIR PATHOGENE</subject><subject>Proprotein Convertase 5</subject><subject>PROTEASAS</subject><subject>PROTEASE</subject><subject>Protein Processing, Post-Translational - genetics</subject><subject>PROTEOLISIS</subject><subject>PROTEOLYSE</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Substrate Specificity</subject><subject>Subtilisins - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Vaccinia virus - genetics</subject><subject>VIRUS DE LA INFLUENZA AVIAR</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGP1CAYxRujWcfVqwcTE07eOgItLRwn4647ySYeZtcrAfp1RCldgY4Z_6n9F6V29GY8EfJ-7_vgvaJ4TfCaYNy8P9owrokQbE2qpnpSrAgWTYmrmjwtVhjXtGw4pc-LFzF-xfnetviiuGgbwiknq-Lx7gugGxjU4eCmZL31aOtAHZW2zqYTGnuk0GcbJgc-oc3RKo92vncT-J-LEJE-of2kUzZE60tnvwG68t34EMYEKkJEu_jHY6Cb8ZSXbgbrR7QxtkO7YYDOqgTuhD6MP3xMAdQw757B5T0HQHub4GXxrFcuwqvzeVncX1_dbW_K208fd9vNbWlqKlJZ1w1nLXAsuKE17zrglQFCVUOzpGslOt2bFipdVZ2mhCkstBKk1UzQVvTVZfFumZt_8X2CmORgowHnlIdxirJta0wqzP8LkobXTDCRwfUCmjDGGKCXD8EOKpwkwXKuUs5VyrlKOVeZDW_Pkyed8_mLn7vL-ptF79Uo1SHYKO_3gjHOWJtFvoiQQzpaCDIa-zt_G8Ak2Y32X3t_AeGpuH4</recordid><startdate>19950710</startdate><enddate>19950710</enddate><creator>Horimoto, Taisuke</creator><creator>Kawaoka, Yoshihiro</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19950710</creationdate><title>The Hemagglutinin Cleavability of a Virulent Avian Influenza Virus by Subtilisin-like Endoproteases Is Influenced by the Amino Acid Immediately Downstream of the Cleavage Site</title><author>Horimoto, Taisuke ; Kawaoka, Yoshihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-446857e8098c248dde83ce12a62446b4a9dbfc7e3b33db215a09ba917b59279f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>AGGLUTININE</topic><topic>AGLUTININAS</topic><topic>Amino Acid Sequence</topic><topic>Amino Acids - physiology</topic><topic>COMPOSICION QUIMICA</topic><topic>COMPOSITION CHIMIQUE</topic><topic>Furin</topic><topic>glycine</topic><topic>Hemagglutinins, Viral - genetics</topic><topic>Hemagglutinins, Viral - metabolism</topic><topic>Influenza A virus - enzymology</topic><topic>Influenza A virus - genetics</topic><topic>Influenza A virus - metabolism</topic><topic>INFLUENZAVIRUS AVIAIRE</topic><topic>Molecular Sequence Data</topic><topic>MUTACION</topic><topic>MUTATION</topic><topic>Mutation - physiology</topic><topic>PODER PATOGENO</topic><topic>POUVOIR PATHOGENE</topic><topic>Proprotein Convertase 5</topic><topic>PROTEASAS</topic><topic>PROTEASE</topic><topic>Protein Processing, Post-Translational - genetics</topic><topic>PROTEOLISIS</topic><topic>PROTEOLYSE</topic><topic>Serine Endopeptidases - metabolism</topic><topic>Substrate Specificity</topic><topic>Subtilisins - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Vaccinia virus - genetics</topic><topic>VIRUS DE LA INFLUENZA AVIAR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horimoto, Taisuke</creatorcontrib><creatorcontrib>Kawaoka, Yoshihiro</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horimoto, Taisuke</au><au>Kawaoka, Yoshihiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Hemagglutinin Cleavability of a Virulent Avian Influenza Virus by Subtilisin-like Endoproteases Is Influenced by the Amino Acid Immediately Downstream of the Cleavage Site</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>1995-07-10</date><risdate>1995</risdate><volume>210</volume><issue>2</issue><spage>466</spage><epage>470</epage><pages>466-470</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Many viral membrane glycoproteins are post-translationally processed by intracellular endoproteases such as subtilisin-like proteases. These proteases recognize a cleavage site sequence comprising basic amino acids positioned upstream of the cleavage site of the viral proteins. Here, we mutated the glycine residue immediately downstream of the cleavage site (P1) of hemagglutinin (HA) from a virulent avian influenza virus, A/turkey/Ontario/7732/66 (H5N9) (R-R-R-K-K-R/G), to examine the effect of this mutation on its clevability. Substitution of Gly with Ile, Leu, Val, or Pro, but not Ala, Asp, Phe, His, Ser, or Thr, resulted in substantial reduction of HA cleavage by endogenous endoproteases in CV-1 cells and by vaccinia-expressed PC6 and, albeit to a lesser extent, furin. We conclude that HA cleavage by subtilisin-like proteases is influenced by the downstream P1 amino acid in the absence of upstream cleavage site sequence alterations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>7618281</pmid><doi>10.1006/viro.1995.1363</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Virology (New York, N.Y.), 1995-07, Vol.210 (2), p.466-470 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | AGGLUTININE AGLUTININAS Amino Acid Sequence Amino Acids - physiology COMPOSICION QUIMICA COMPOSITION CHIMIQUE Furin glycine Hemagglutinins, Viral - genetics Hemagglutinins, Viral - metabolism Influenza A virus - enzymology Influenza A virus - genetics Influenza A virus - metabolism INFLUENZAVIRUS AVIAIRE Molecular Sequence Data MUTACION MUTATION Mutation - physiology PODER PATOGENO POUVOIR PATHOGENE Proprotein Convertase 5 PROTEASAS PROTEASE Protein Processing, Post-Translational - genetics PROTEOLISIS PROTEOLYSE Serine Endopeptidases - metabolism Substrate Specificity Subtilisins - metabolism Tumor Cells, Cultured Vaccinia virus - genetics VIRUS DE LA INFLUENZA AVIAR |
| title | The Hemagglutinin Cleavability of a Virulent Avian Influenza Virus by Subtilisin-like Endoproteases Is Influenced by the Amino Acid Immediately Downstream of the Cleavage Site |
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