Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication
Identifieur interne : 000118 ( 1968/Analysis ); précédent : 000117; suivant : 000119Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication
Auteurs : Takashi Suzuki [Japon] ; Tadanobu Takahashi [Japon] ; Chao-Tan Guo [Japon, République populaire de Chine] ; Kazuya I.-P. Jwa Hidari [Japon] ; Daisei Miyamoto [Japon] ; Hideo Goto [Japon] ; Yoshihiro Kawaoka [Japon, États-Unis] ; Yasuo Suzuki [Japon]Source :
- Journal of virology [ 0022-538X ] ; 2005.
Descripteurs français
- KwdFr :
- Acides sialiques (pharmacologie), Animaux, Antienzymes (pharmacologie), Chiens, Concentration en ions d'hydrogène, Endocytose, Grippe humaine (virologie), Guanidines, Humains, Lignée cellulaire, Mâle, Pyrannes, Réplication virale (), Réplication virale (génétique), Réplication virale (physiologie), Sialidase (antagonistes et inhibiteurs), Sialidase (génétique), Sialidase (métabolisme), Souris, Souris de lignée C57BL, Stabilité enzymatique, Transfection, Virus de la grippe A (), Virus de la grippe A (enzymologie), Virus de la grippe A (génétique), Virus de la grippe A (physiologie), Zanamivir.
- MESH :
- antagonistes et inhibiteurs : Sialidase.
- enzymologie : Virus de la grippe A.
- génétique : Réplication virale, Sialidase, Virus de la grippe A.
- métabolisme : Sialidase.
- pharmacologie : Acides sialiques, Antienzymes.
- physiologie : Réplication virale, Virus de la grippe A.
- virologie : Grippe humaine.
- Pascal (Inist)
- Animaux, Chiens, Concentration en ions d'hydrogène, Endocytose, Guanidines, Humains, Lignée cellulaire, Mâle, Pyrannes, Réplication virale, Souris, Souris de lignée C57BL, Stabilité enzymatique, Transfection, Virus de la grippe A, Virus grippal A, Exo-α-sialidase, Endocytose, Réplication, Microbiologie, Virologie, Zanamivir.
English descriptors
- KwdEn :
- Animals, Cell Line, Dogs, Endocytosis, Enzyme Inhibitors (pharmacology), Enzyme Stability, Exo-α-sialidase, Guanidines, Humans, Hydrogen-Ion Concentration, Influenza A virus, Influenza A virus (drug effects), Influenza A virus (enzymology), Influenza A virus (genetics), Influenza A virus (physiology), Influenza, Human (virology), Male, Mice, Mice, Inbred C57BL, Microbiology, Neuraminidase (antagonists & inhibitors), Neuraminidase (genetics), Neuraminidase (metabolism), Pyrans, Replication, Sialic Acids (pharmacology), Transfection, Virology, Virus Replication (drug effects), Virus Replication (genetics), Virus Replication (physiology), Zanamivir.
- MESH :
- chemical , antagonists & inhibitors : Neuraminidase.
- chemical , genetics : Neuraminidase.
- chemical , metabolism : Neuraminidase.
- chemical , pharmacology : Enzyme Inhibitors, Sialic Acids.
- drug effects : Influenza A virus, Virus Replication.
- enzymology : Influenza A virus.
- genetics : Influenza A virus, Virus Replication.
- physiology : Influenza A virus, Virus Replication.
- virology : Influenza, Human.
- Animals, Cell Line, Dogs, Endocytosis, Enzyme Stability, Guanidines, Humans, Hydrogen-Ion Concentration, Male, Mice, Mice, Inbred C57BL, Pyrans, Transfection, Zanamivir.
Abstract
N2 neuraminidase (NA) genes of the 1957 and 1968 pandemic influenza virus strains possessed avian-like low-pH stability of sialidase activity, unlike most epidemic strains. We generated four reverse-genetics viruses from a genetic background of A/WSN/33 (H1N1) that included parental N2 NAs of 1968 pandemic (H3N2) and epidemic (H2N2) strains or their counterpart N2 NAs in which the low-pH stability of the sialidase activity was changed by substitutions of one or two amino acid residues. We found that the transfectant viruses bearing low-pH-stable sialidase (WSN/Stable-NAs) showed 25- to 80-times-greater ability to replicate in Madin-Darby canine kidney (MDCK) cells than did the transfectant viruses bearing low-pH-unstable sialidase (WSN/ Unstable-NAs). Enzymatic activities of WSN/Stable-NAs were detected in endosomes of MDCK cells after 90 min of virus internalization by in situ fluorescent detection with 5-bromo-4-chloro-indole-3-yl-α-N-acetylneuraminic acid and Fast Red Violet LB. Inhibition of sialidase activity of WSN/Stable-NAs on the endocytic pathway by pretreatment with 4-guanidino-2,4-dideoxy-N-acetylneuraminic acid (zanamivir) resulted in a significant decrease in progeny viruses. In contrast, the enzymatic activities of WSN/Unstable-NAs, the replication of which had no effect on pretreatment with zanamivir, were undetectable in cells under the same conditions. Hemadsorption assays of transfectant-virus-infected cells revealed that the low-pH stability of the sialidase had no effect on the process of removal of sialic acid from hemagglutinin in the Golgi regions. Moreover, high titers of viruses were recovered from the lungs of mice infected with WSN/Stable-NAs on day 3 after intranasal inoculation, but WSN/Unstable-NAs were cleared from the lungs of the mice. These results indicate that sialidase activity in late endosome/lysosome traffic enhances influenza A virus replication.
Url:
Affiliations:
- Japon, République populaire de Chine, États-Unis
- Région de Kantō, Wisconsin
- Madison (Wisconsin), Tokyo
- Université de Tokyo, Université du Wisconsin à Madison
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Links to Exploration step
Pascal:05-0406988Le document en format XML
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replication</title><author><name sortKey="Suzuki, Takashi" sort="Suzuki, Takashi" uniqKey="Suzuki T" first="Takashi" last="Suzuki">Takashi Suzuki</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation></author><author><name sortKey="Takahashi, Tadanobu" sort="Takahashi, Tadanobu" uniqKey="Takahashi T" first="Tadanobu" last="Takahashi">Tadanobu Takahashi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation></author><author><name sortKey="Guo, Chao Tan" sort="Guo, Chao Tan" uniqKey="Guo C" first="Chao-Tan" last="Guo">Chao-Tan Guo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institute of Bioengineering, Zhejiang Academy of Medical Sciences</s1><s2>Hang Zhou</s2><s3>CHN</s3><sZ>3 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hang Zhou</wicri:noRegion></affiliation></author><author><name sortKey="Jwa Hidari, Kazuya I P" sort="Jwa Hidari, Kazuya I P" uniqKey="Jwa Hidari K" first="Kazuya I.-P." last="Jwa Hidari">Kazuya I.-P. Jwa Hidari</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation></author><author><name sortKey="Miyamoto, Daisei" sort="Miyamoto, Daisei" uniqKey="Miyamoto D" first="Daisei" last="Miyamoto">Daisei Miyamoto</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation></author><author><name sortKey="Goto, Hideo" sort="Goto, Hideo" uniqKey="Goto H" first="Hideo" last="Goto">Hideo Goto</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>International Research Center for Infectious Diseases</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>7 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Pathobiological Sciences, University of Wisconsin-Madison</s1><s2>Madison, Wisconsin</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Wisconsin</region></placeName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName><orgName type="university" n="3">Université du Wisconsin à Madison</orgName></affiliation></author><author><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences and COE Program in the 21st Century</s1><s2>Shizuoka</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Shizuoka</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>CREST, Japan Science and Technology Agency</s1><s2>Saitama</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Saitama</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Dogs</term><term>Endocytosis</term><term>Enzyme Inhibitors (pharmacology)</term><term>Enzyme Stability</term><term>Exo-α-sialidase</term><term>Guanidines</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Influenza A virus</term><term>Influenza A virus (drug effects)</term><term>Influenza A virus (enzymology)</term><term>Influenza A virus (genetics)</term><term>Influenza A virus (physiology)</term><term>Influenza, Human (virology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Microbiology</term><term>Neuraminidase (antagonists & inhibitors)</term><term>Neuraminidase (genetics)</term><term>Neuraminidase (metabolism)</term><term>Pyrans</term><term>Replication</term><term>Sialic Acids (pharmacology)</term><term>Transfection</term><term>Virology</term><term>Virus Replication (drug effects)</term><term>Virus Replication (genetics)</term><term>Virus Replication (physiology)</term><term>Zanamivir</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides sialiques (pharmacologie)</term><term>Animaux</term><term>Antienzymes (pharmacologie)</term><term>Chiens</term><term>Concentration en ions d'hydrogène</term><term>Endocytose</term><term>Grippe humaine (virologie)</term><term>Guanidines</term><term>Humains</term><term>Lignée cellulaire</term><term>Mâle</term><term>Pyrannes</term><term>Réplication virale ()</term><term>Réplication virale (génétique)</term><term>Réplication virale (physiologie)</term><term>Sialidase (antagonistes et inhibiteurs)</term><term>Sialidase (génétique)</term><term>Sialidase (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Stabilité enzymatique</term><term>Transfection</term><term>Virus de la grippe A ()</term><term>Virus de la grippe A (enzymologie)</term><term>Virus de la grippe A (génétique)</term><term>Virus de la grippe A (physiologie)</term><term>Zanamivir</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Neuraminidase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Neuraminidase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Neuraminidase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term><term>Sialic Acids</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Sialidase</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Influenza A virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Réplication virale</term><term>Sialidase</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Sialidase</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acides sialiques</term><term>Antienzymes</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Réplication virale</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Dogs</term><term>Endocytosis</term><term>Enzyme Stability</term><term>Guanidines</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Pyrans</term><term>Transfection</term><term>Zanamivir</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Chiens</term><term>Concentration en ions d'hydrogène</term><term>Endocytose</term><term>Guanidines</term><term>Humains</term><term>Lignée cellulaire</term><term>Mâle</term><term>Pyrannes</term><term>Réplication virale</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Stabilité enzymatique</term><term>Transfection</term><term>Virus de la grippe A</term><term>Virus grippal A</term><term>Exo-α-sialidase</term><term>Endocytose</term><term>Réplication</term><term>Microbiologie</term><term>Virologie</term><term>Zanamivir</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">N2 neuraminidase (NA) genes of the 1957 and 1968 pandemic influenza virus strains possessed avian-like low-pH stability of sialidase activity, unlike most epidemic strains. We generated four reverse-genetics viruses from a genetic background of A/WSN/33 (H1N1) that included parental N2 NAs of 1968 pandemic (H3N2) and epidemic (H2N2) strains or their counterpart N2 NAs in which the low-pH stability of the sialidase activity was changed by substitutions of one or two amino acid residues. We found that the transfectant viruses bearing low-pH-stable sialidase (WSN/Stable-NAs) showed 25- to 80-times-greater ability to replicate in Madin-Darby canine kidney (MDCK) cells than did the transfectant viruses bearing low-pH-unstable sialidase (WSN/ Unstable-NAs). Enzymatic activities of WSN/Stable-NAs were detected in endosomes of MDCK cells after 90 min of virus internalization by in situ fluorescent detection with 5-bromo-4-chloro-indole-3-yl-α-N-acetylneuraminic acid and Fast Red Violet LB. Inhibition of sialidase activity of WSN/Stable-NAs on the endocytic pathway by pretreatment with 4-guanidino-2,4-dideoxy-N-acetylneuraminic acid (zanamivir) resulted in a significant decrease in progeny viruses. In contrast, the enzymatic activities of WSN/Unstable-NAs, the replication of which had no effect on pretreatment with zanamivir, were undetectable in cells under the same conditions. Hemadsorption assays of transfectant-virus-infected cells revealed that the low-pH stability of the sialidase had no effect on the process of removal of sialic acid from hemagglutinin in the Golgi regions. Moreover, high titers of viruses were recovered from the lungs of mice infected with WSN/Stable-NAs on day 3 after intranasal inoculation, but WSN/Unstable-NAs were cleared from the lungs of the mice. These results indicate that sialidase activity in late endosome/lysosome traffic enhances influenza A virus replication.</div></front></TEI><affiliations><list><country><li>Japon</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Région de Kantō</li><li>Wisconsin</li></region><settlement><li>Madison (Wisconsin)</li><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li><li>Université du Wisconsin à Madison</li></orgName></list><tree><country name="Japon"><noRegion><name sortKey="Suzuki, Takashi" sort="Suzuki, Takashi" uniqKey="Suzuki T" first="Takashi" last="Suzuki">Takashi Suzuki</name></noRegion><name sortKey="Goto, Hideo" sort="Goto, Hideo" uniqKey="Goto H" first="Hideo" last="Goto">Hideo Goto</name><name sortKey="Goto, Hideo" sort="Goto, Hideo" uniqKey="Goto H" first="Hideo" last="Goto">Hideo Goto</name><name sortKey="Guo, Chao Tan" sort="Guo, Chao Tan" uniqKey="Guo C" first="Chao-Tan" last="Guo">Chao-Tan Guo</name><name sortKey="Guo, Chao Tan" sort="Guo, Chao Tan" uniqKey="Guo C" first="Chao-Tan" last="Guo">Chao-Tan Guo</name><name sortKey="Jwa Hidari, Kazuya I P" sort="Jwa Hidari, Kazuya I P" uniqKey="Jwa Hidari K" first="Kazuya I.-P." last="Jwa Hidari">Kazuya I.-P. Jwa Hidari</name><name sortKey="Jwa Hidari, Kazuya I P" sort="Jwa Hidari, Kazuya I P" uniqKey="Jwa Hidari K" first="Kazuya I.-P." last="Jwa Hidari">Kazuya I.-P. Jwa Hidari</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name><name sortKey="Miyamoto, Daisei" sort="Miyamoto, Daisei" uniqKey="Miyamoto D" first="Daisei" last="Miyamoto">Daisei Miyamoto</name><name sortKey="Miyamoto, Daisei" sort="Miyamoto, Daisei" uniqKey="Miyamoto D" first="Daisei" last="Miyamoto">Daisei Miyamoto</name><name sortKey="Suzuki, Takashi" sort="Suzuki, Takashi" uniqKey="Suzuki T" first="Takashi" last="Suzuki">Takashi Suzuki</name><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name><name sortKey="Suzuki, Yasuo" sort="Suzuki, Yasuo" uniqKey="Suzuki Y" first="Yasuo" last="Suzuki">Yasuo Suzuki</name><name sortKey="Takahashi, Tadanobu" sort="Takahashi, Tadanobu" uniqKey="Takahashi T" first="Tadanobu" last="Takahashi">Tadanobu Takahashi</name><name sortKey="Takahashi, Tadanobu" sort="Takahashi, Tadanobu" uniqKey="Takahashi T" first="Tadanobu" last="Takahashi">Tadanobu Takahashi</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Guo, Chao Tan" sort="Guo, Chao Tan" uniqKey="Guo C" first="Chao-Tan" last="Guo">Chao-Tan Guo</name></noRegion></country><country name="États-Unis"><region name="Wisconsin"><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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