Persistent Replication of Severe Acute Respiratory Syndrome Coronavirus in Human Tubular Kidney Cells Selects for Adaptive Mutations in the Membrane Protein
Identifieur interne : 003483 ( Main/Exploration ); précédent : 003482; suivant : 003484Persistent Replication of Severe Acute Respiratory Syndrome Coronavirus in Human Tubular Kidney Cells Selects for Adaptive Mutations in the Membrane Protein
Auteurs : Filippo Pacciarini [Italie] ; Silvia Ghezzi [Italie] ; Filippo Canducci [Italie] ; Amy Sims [États-Unis] ; Michela Sampaolo [Italie] ; Elena Ferioli [Italie] ; Massimo Clementi [Italie] ; Guido Poli [Italie] ; Pier Giulio Conaldi [Italie] ; Ralph Baric [États-Unis] ; Elisa Vicenzi [Italie]Source :
- Journal of virology [ 0022-538X ] ; 2008.
Descripteurs français
- KwdFr :
- Adaptation biologique (génétique), Animaux, Cellules épithéliales (enzymologie), Cinétique, Humains, Lignée cellulaire, Mutation (génétique), Peptidyl-Dipeptidase A (génétique), Peptidyl-Dipeptidase A (métabolisme), Protéines de la matrice virale (génétique), Protéines de la matrice virale (métabolisme), Rein (cytologie), Rein (métabolisme), Réplication virale, Survie cellulaire, Virus du SRAS (physiologie).
- MESH :
- cytologie : Rein.
- enzymologie : Cellules épithéliales.
- génétique : Adaptation biologique, Mutation, Peptidyl-Dipeptidase A, Protéines de la matrice virale.
- métabolisme : Peptidyl-Dipeptidase A, Protéines de la matrice virale, Rein.
- physiologie : Virus du SRAS.
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Adaptation, Biological (genetics), Animals, Cell Line, Cell Survival, Chlorocebus aethiops, Coronavirus, Epithelial Cells (enzymology), Human, Humans, In vitro, Kidney, Kidney (cytology), Kidney (metabolism), Kinetics, Membrane protein, Mutation, Mutation (genetics), Peptidyl-Dipeptidase A (genetics), Peptidyl-Dipeptidase A (metabolism), Replication, SARS Virus (physiology), Severe acute respiratory syndrome, Viral Matrix Proteins (genetics), Viral Matrix Proteins (metabolism), Virology, Virus Replication.
- MESH :
- chemical , genetics : Peptidyl-Dipeptidase A, Viral Matrix Proteins.
- cytology : Kidney.
- enzymology : Epithelial Cells.
- genetics : Adaptation, Biological, Mutation.
- metabolism : Kidney, Peptidyl-Dipeptidase A, Viral Matrix Proteins.
- physiology : SARS Virus.
- Animals, Cell Line, Cell Survival, Chlorocebus aethiops, Humans, Kinetics, Virus Replication.
Abstract
Severe acute respiratory syndrome (SARS) is a systemic disease characterized by both lung pathology and widespread extrapulmonary virus dissemination causing multiple organ injuries. In this regard, renal dysfunction is an ominous sign in patients with SARS. Indeed, clusters of SARS coronavirus (SARS-CoV) particles have been detected in the cytoplasm of renal tubular epithelial cells in postmortem studies, explaining the presence of infectious virus in the urine of SARS patients. In order to investigate the potential SARS-CoV kidney tropism, we have evaluated the susceptibility of human renal cells of tubular and glomerular origin to in vitro SARS-CoV infection. Immortalized cultures of differentiated proximal tubular epithelial cells (PTEC), glomerular mesangial cells (MC), and glomerular epithelial cells (podocytes) were found to express the SARS-CoV receptor angiotensin-converting enzyme 2 on their surface. Productive infection, however, occurred only in PTEC but not in glomerular cells. A transient infection with poor virus production was observed in MC, whereas podocytes were not permissive to SARS-CoV infection. In contrast to the cytopathic infection of the Vero E6 cell line, SARS-CoV did not cause overt cytopathic effects in PTEC or MC. Of interest, PTEC, but not MC, maintained stable levels of SARS-CoV production in serial subcultures, suggesting a persistent state of infection. In this regard, a SARS-CoV variant with increased replication capacity in PTEC was selected after four serial subculture passages. This SARS-CoV variant acquired a single nonconservative amino acid change from glutamic acid (E) to alanine (A) at position 11 in the viral membrane (M) protein. The E11A point mutation was sufficient for enhanced SARS-CoV replication and persistence in PTEC when introduced in a SARS-CoV recombinant infectious clone. These findings indicate that human PTEC may represent a site of SARS-CoV productive and persistent replication favoring the emergence of viral variants with increased replication capacity, at least in these kidney cells.
Url:
Affiliations:
- Italie, États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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Le document en format XML
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Replication of Severe Acute Respiratory Syndrome Coronavirus in Human Tubular Kidney Cells Selects for Adaptive Mutations in the Membrane Protein</title><author><name sortKey="Pacciarini, Filippo" sort="Pacciarini, Filippo" uniqKey="Pacciarini F" first="Filippo" last="Pacciarini">Filippo Pacciarini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Ghezzi, Silvia" sort="Ghezzi, Silvia" uniqKey="Ghezzi S" first="Silvia" last="Ghezzi">Silvia Ghezzi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Canducci, Filippo" sort="Canducci, Filippo" uniqKey="Canducci F" first="Filippo" last="Canducci">Filippo Canducci</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Microbiology and Virology, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Vita-Salute San Raffaele University, School of Medicine</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Sims, Amy" sort="Sims, Amy" uniqKey="Sims A" first="Amy" last="Sims">Amy Sims</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Sampaolo, Michela" sort="Sampaolo, Michela" uniqKey="Sampaolo M" first="Michela" last="Sampaolo">Michela Sampaolo</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Microbiology and Virology, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Vita-Salute San Raffaele University, School of Medicine</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Ferioli, Elena" sort="Ferioli, Elena" uniqKey="Ferioli E" first="Elena" last="Ferioli">Elena Ferioli</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Medicine and Public Health, University of Insubria</s1><s2>Varese</s2><s3>ITA</s3><sZ>6 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Varese</wicri:noRegion></affiliation></author><author><name sortKey="Clementi, Massimo" sort="Clementi, Massimo" uniqKey="Clementi M" first="Massimo" last="Clementi">Massimo Clementi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Microbiology and Virology, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Vita-Salute San Raffaele University, School of Medicine</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Poli, Guido" sort="Poli, Guido" uniqKey="Poli G" first="Guido" last="Poli">Guido Poli</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Vita-Salute San Raffaele University, School of Medicine</s1><s2>Milano</s2><s3>ITA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</wicri:noRegion></affiliation></author><author><name sortKey="Giulio Conaldi, Pier" sort="Giulio Conaldi, Pier" uniqKey="Giulio Conaldi P" first="Pier" last="Giulio Conaldi">Pier Giulio Conaldi</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Laboratory of Clinical Pathology, Microbiology and Virology, Mediterranean Institute for Transplantation and Advanced Specialised Therapies, University of Pittsburgh Medical Center-Italy</s1><s2>Palermo</s2><s3>ITA</s3><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Palermo</wicri:noRegion></affiliation></author><author><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Vicenzi, Elisa" sort="Vicenzi, Elisa" uniqKey="Vicenzi E" first="Elisa" last="Vicenzi">Elisa Vicenzi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute</s1><s2>Milano</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Milano</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="2008">2008</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>Adaptation, Biological (genetics)</term><term>Animals</term><term>Cell Line</term><term>Cell Survival</term><term>Chlorocebus aethiops</term><term>Coronavirus</term><term>Epithelial Cells (enzymology)</term><term>Human</term><term>Humans</term><term>In vitro</term><term>Kidney</term><term>Kidney (cytology)</term><term>Kidney (metabolism)</term><term>Kinetics</term><term>Membrane protein</term><term>Mutation</term><term>Mutation (genetics)</term><term>Peptidyl-Dipeptidase A (genetics)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>Replication</term><term>SARS Virus (physiology)</term><term>Severe acute respiratory syndrome</term><term>Viral Matrix Proteins (genetics)</term><term>Viral Matrix Proteins (metabolism)</term><term>Virology</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adaptation biologique (génétique)</term><term>Animaux</term><term>Cellules épithéliales (enzymologie)</term><term>Cinétique</term><term>Humains</term><term>Lignée cellulaire</term><term>Mutation (génétique)</term><term>Peptidyl-Dipeptidase A (génétique)</term><term>Peptidyl-Dipeptidase A (métabolisme)</term><term>Protéines de la matrice virale (génétique)</term><term>Protéines de la matrice virale (métabolisme)</term><term>Rein (cytologie)</term><term>Rein (métabolisme)</term><term>Réplication virale</term><term>Survie cellulaire</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptidyl-Dipeptidase A</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Rein</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Kidney</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Cellules épithéliales</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Epithelial Cells</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adaptation, Biological</term><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adaptation biologique</term><term>Mutation</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de la matrice virale</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Kidney</term><term>Peptidyl-Dipeptidase A</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term><term>Protéines de la matrice virale</term><term>Rein</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Cell Survival</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Kinetics</term><term>Virus Replication</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Cinétique</term><term>Coronavirus</term><term>Homme</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication</term><term>Rein</term><term>In vitro</term><term>Mutation</term><term>Protéine membranaire</term><term>Réplication virale</term><term>Survie cellulaire</term><term>Virologie</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a systemic disease characterized by both lung pathology and widespread extrapulmonary virus dissemination causing multiple organ injuries. In this regard, renal dysfunction is an ominous sign in patients with SARS. Indeed, clusters of SARS coronavirus (SARS-CoV) particles have been detected in the cytoplasm of renal tubular epithelial cells in postmortem studies, explaining the presence of infectious virus in the urine of SARS patients. In order to investigate the potential SARS-CoV kidney tropism, we have evaluated the susceptibility of human renal cells of tubular and glomerular origin to in vitro SARS-CoV infection. Immortalized cultures of differentiated proximal tubular epithelial cells (PTEC), glomerular mesangial cells (MC), and glomerular epithelial cells (podocytes) were found to express the SARS-CoV receptor angiotensin-converting enzyme 2 on their surface. Productive infection, however, occurred only in PTEC but not in glomerular cells. A transient infection with poor virus production was observed in MC, whereas podocytes were not permissive to SARS-CoV infection. In contrast to the cytopathic infection of the Vero E6 cell line, SARS-CoV did not cause overt cytopathic effects in PTEC or MC. Of interest, PTEC, but not MC, maintained stable levels of SARS-CoV production in serial subcultures, suggesting a persistent state of infection. In this regard, a SARS-CoV variant with increased replication capacity in PTEC was selected after four serial subculture passages. This SARS-CoV variant acquired a single nonconservative amino acid change from glutamic acid (E) to alanine (A) at position 11 in the viral membrane (M) protein. The E11A point mutation was sufficient for enhanced SARS-CoV replication and persistence in PTEC when introduced in a SARS-CoV recombinant infectious clone. These findings indicate that human PTEC may represent a site of SARS-CoV productive and persistent replication favoring the emergence of viral variants with increased replication capacity, at least in these kidney cells.</div></front></TEI><affiliations><list><country><li>Italie</li><li>États-Unis</li></country><region><li>Caroline du Nord</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li></settlement><orgName><li>Université de Caroline du Nord à Chapel Hill</li></orgName></list><tree><country name="Italie"><noRegion><name sortKey="Pacciarini, Filippo" sort="Pacciarini, Filippo" uniqKey="Pacciarini F" first="Filippo" last="Pacciarini">Filippo Pacciarini</name></noRegion><name sortKey="Canducci, Filippo" sort="Canducci, Filippo" uniqKey="Canducci F" first="Filippo" last="Canducci">Filippo Canducci</name><name sortKey="Canducci, Filippo" sort="Canducci, Filippo" uniqKey="Canducci F" first="Filippo" last="Canducci">Filippo Canducci</name><name sortKey="Clementi, Massimo" sort="Clementi, Massimo" uniqKey="Clementi M" first="Massimo" last="Clementi">Massimo Clementi</name><name sortKey="Clementi, Massimo" sort="Clementi, Massimo" uniqKey="Clementi M" first="Massimo" last="Clementi">Massimo Clementi</name><name sortKey="Ferioli, Elena" sort="Ferioli, Elena" uniqKey="Ferioli E" first="Elena" last="Ferioli">Elena Ferioli</name><name sortKey="Ghezzi, Silvia" sort="Ghezzi, Silvia" uniqKey="Ghezzi S" first="Silvia" last="Ghezzi">Silvia Ghezzi</name><name sortKey="Giulio Conaldi, Pier" sort="Giulio Conaldi, Pier" uniqKey="Giulio Conaldi P" first="Pier" last="Giulio Conaldi">Pier Giulio Conaldi</name><name sortKey="Poli, Guido" sort="Poli, Guido" uniqKey="Poli G" first="Guido" last="Poli">Guido Poli</name><name sortKey="Poli, Guido" sort="Poli, Guido" uniqKey="Poli G" first="Guido" last="Poli">Guido Poli</name><name sortKey="Sampaolo, Michela" sort="Sampaolo, Michela" uniqKey="Sampaolo M" first="Michela" last="Sampaolo">Michela Sampaolo</name><name sortKey="Sampaolo, Michela" sort="Sampaolo, Michela" uniqKey="Sampaolo M" first="Michela" last="Sampaolo">Michela Sampaolo</name><name sortKey="Vicenzi, Elisa" sort="Vicenzi, Elisa" uniqKey="Vicenzi E" first="Elisa" last="Vicenzi">Elisa Vicenzi</name></country><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Sims, Amy" sort="Sims, Amy" uniqKey="Sims A" first="Amy" last="Sims">Amy Sims</name></region><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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