Identification Of Novel Functional Regions Within The Spike Glycoprotein Of MHV-A59 Based On A Bioinformatics Approach
Identifieur interne : 000A30 ( Main/Exploration ); précédent : 000A29; suivant : 000A31Identification Of Novel Functional Regions Within The Spike Glycoprotein Of MHV-A59 Based On A Bioinformatics Approach
Auteurs : Gili Kaufman [États-Unis] ; Pinghua Liu [États-Unis] ; Julian L. Leibowitz [États-Unis]Source :
- Virus research [ 0168-1702 ] ; 2014.
Abstract
Mouse Hepatitis Virus (MHV) is a single-stranded positive sense RNA virus with the ability to promote acute and chronic diseases in mice. The MHV spike protein (S) is a major virulence determinant which in addition to binding to cellular receptors to mediate cell entry and facilitate virus spread to adjacent cells by cell-cell fusion, also is a molecular mimic of the FcγRII receptor. This molecular mimicry of FcγRII by the MHV S protein is also exhibited by other lineage 2a betacoronaviruses, with the exception of the human coronavirus HCoV-OC43. In this work we undertook a mutational analysis to attempt to identify specific amino acid sequences within the spike glycoprotein crucial for molecular mimicry of FcγRII. Although we were unsuccessful in isolating mutant viruses which were specifically defective in that property, we identified several mutations with interesting phenotypes. Mutation of the cysteine in position 547 to alanine and alanine replacements at residues 581–586 was lethal. Replacing proline 939 with the corresponding HCoV-OC43 residue, leucine, decreased the ability MHV to induce cell-cell fusion, providing experimental support for an earlier proposal that residues 929–944 make up the fusion peptide of the MHV S protein.
Url:
DOI: 10.1016/j.virusres.2014.05.023
PubMed: 24910120
PubMed Central: 4134989
Affiliations:
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MHV-A59 Based On A Bioinformatics Approach</title><author><name sortKey="Kaufman, Gili" sort="Kaufman, Gili" uniqKey="Kaufman G" first="Gili" last="Kaufman">Gili Kaufman</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station, TX 77843-1114 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Pinghua" sort="Liu, Pinghua" uniqKey="Liu P" first="Pinghua" last="Liu">Pinghua Liu</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station, TX 77843-1114 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station</wicri:cityArea></affiliation></author><author><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L." last="Leibowitz">Julian L. Leibowitz</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station, TX 77843-1114 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Microbial Pathogenesis and Immunology, Texas A&M University, College of Medicine, College Station</wicri:cityArea></affiliation></author></analytic><series><title level="j">Virus research</title><idno type="ISSN">0168-1702</idno><idno type="eISSN">1872-7492</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Mouse Hepatitis Virus (MHV) is a single-stranded positive sense RNA virus with
the ability to promote acute and chronic diseases in mice. The MHV spike protein (S) is a
major virulence determinant which in addition to binding to cellular receptors to mediate
cell entry and facilitate virus spread to adjacent cells by cell-cell fusion, also is a
molecular mimic of the FcγRII receptor. This molecular mimicry of FcγRII
by the MHV S protein is also exhibited by other lineage 2a betacoronaviruses, with the
exception of the human coronavirus HCoV-OC43. In this work we undertook a mutational
analysis to attempt to identify specific amino acid sequences within the spike
glycoprotein crucial for molecular mimicry of FcγRII. Although we were
unsuccessful in isolating mutant viruses which were specifically defective in that
property, we identified several mutations with interesting phenotypes. Mutation of the
cysteine in position 547 to alanine and alanine replacements at residues 581–586
was lethal. Replacing proline 939 with the corresponding HCoV-OC43 residue, leucine,
decreased the ability MHV to induce cell-cell fusion, providing experimental support for
an earlier proposal that residues 929–944 make up the fusion peptide of the MHV S
protein.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Kaufman, Gili" sort="Kaufman, Gili" uniqKey="Kaufman G" first="Gili" last="Kaufman">Gili Kaufman</name></region><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L." last="Leibowitz">Julian L. Leibowitz</name><name sortKey="Liu, Pinghua" sort="Liu, Pinghua" uniqKey="Liu P" first="Pinghua" last="Liu">Pinghua Liu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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