Genetic and structural analysis of a virulence determinant in polyomavirus VP1

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Published inJournal of Virology Vol. 69; no. 12; pp. 7925 - 7931
Main Authors Bauer, P H, Bronson, R T, Fung, S C, Freund, R, Stehle, T, Harrison, S C, Benjamin, T L
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.12.1995
Subjects
Animals
Animals, Newborn
Capsid - chemistry
Capsid - genetics
Capsid Proteins
Crystallography, X-Ray
Genes, Viral
Genotype
Mice
Mice, Inbred C3H
Molecular Sequence Data
Mutagenesis, Site-Directed
Organ Specificity
Polyomavirus - genetics
Polyomavirus - isolation & purification
Polyomavirus - pathogenicity
Polyomavirus Infections - pathology
Polyomavirus Infections - physiopathology
Receptors, Virus - physiology
Species Specificity
Tumor Virus Infections - pathology
Tumor Virus Infections - physiopathology
Virulence - genetics
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Abstract Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
AbstractList The LID strain of polyomavirus differs from other laboratory strains in causing a rapidly lethal infection of newborn C3H/Bi mice. This virulent behavior of LID was attenuated by dilution, yet at sublethal doses LID was able to induce tumors at a high frequency, like its parent virus PTA. By constructing and assaying LID-PTA recombinant viruses and by DNA sequencing, the determinant of virulence in LID was mapped to the major viral capsid protein, VP1. The VP1s of LID and PTA differed at two positions: at 185, LID has phenylalanine and PTA has tyrosine, and at 296, LID has alanine and PTA has valine. Results obtained with viruses constructed by site-directed mutagenesis showed that alanine at position 296 is sufficient to confer a fully virulent phenotype regardless of which amino acid is at position 185. However, with valine at position 296, an effect of phenylalanine at position 185 is apparent, as this virus possesses an intermediate level of virulence. A crystal structure of polyomavirus complexed with 3'-sialyl lactose previously indicated van der Waals contacts between the side chain of valine 296 and the sialic acid ring (T. Stehle, Y. Yan, T. L. Benjamin, and S. C. Harrison, Nature [London] 369:160-163, 1994). When this interaction was modeled with alanine, these contacts were greatly reduced. Direct confirmation that the substitutions in VP1 affected receptor binding was obtained by studying virus hemagglutination behavior. The ensemble of results are discussed in terms of the idea that a lower affinity of the virus for its receptor can result in more rapid spread and increased pathogenicity.
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Author S C Fung
R Freund
R T Bronson
T Stehle
T L Benjamin
P H Bauer
S C Harrison
AuthorAffiliation Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
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Snippet Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley...
The LID strain of polyomavirus differs from other laboratory strains in causing a rapidly lethal infection of newborn C3H/Bi mice. This virulent behavior of...
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SubjectTerms Animals
Animals, Newborn
Capsid - chemistry
Capsid - genetics
Capsid Proteins
Crystallography, X-Ray
Genes, Viral
Genotype
Mice
Mice, Inbred C3H
Molecular Sequence Data
Mutagenesis, Site-Directed
Organ Specificity
Polyomavirus - genetics
Polyomavirus - isolation & purification
Polyomavirus - pathogenicity
Polyomavirus Infections - pathology
Polyomavirus Infections - physiopathology
Receptors, Virus - physiology
Species Specificity
Tumor Virus Infections - pathology
Tumor Virus Infections - physiopathology
Virulence - genetics
Title Genetic and structural analysis of a virulence determinant in polyomavirus VP1
URI http://jvi.asm.org/content/69/12/7925.abstract
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Volume 69
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