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An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity.
Monticelli, Stephanie R; Bryk, Peter; Brewer, Matthew G; Aguilar, Hector C; Norbury, Christopher C; Ward, Brian M.
Afiliação
  • Monticelli SR; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
  • Bryk P; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
  • Brewer MG; Department of Dermatology, University of Rochester Medical Center, Rochester, New York, United States of America.
  • Aguilar HC; Department of Microbiology and Immunology, Cornell University, Ithaca, New York, United States of America.
  • Norbury CC; Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
  • Ward BM; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
PLoS Pathog ; 17(12): e1010177, 2021 12.
Article em En | MEDLINE | ID: mdl-34962975
The extracellular virion (EV) form of Orthopoxviruses is required for cell-to-cell spread and pathogenesis, and is the target of neutralizing antibodies in the protective immune response. EV have a double envelope that contains several unique proteins that are involved in its intracellular envelopment and/or subsequent infectivity. One of these, F13, is involved in both EV formation and infectivity. Here, we report that replacement of vaccinia virus F13L with the molluscum contagiosum virus homolog, MC021L, results in the production of EV particles with significantly increased levels of EV glycoproteins, which correlate with a small plaque phenotype. Using a novel fluorescence-activated virion sorting assay to isolate EV populations based on glycoprotein content we determine that EV containing either higher or lower levels of glycoproteins are less infectious, suggesting that there is an optimal concentration of glycoproteins in the outer envelope that is required for maximal infectivity of EV. This optimal glycoprotein concentration was required for lethality and induction of pathology in a cutaneous model of animal infection, but was not required for induction of a protective immune response. Therefore, our results demonstrate that there is a sensitive balance between glycoprotein incorporation, infectivity, and pathogenesis, and that manipulation of EV glycoprotein levels can produce vaccine vectors in which pathologic side effects are attenuated without a marked diminution in induction of protective immunity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacínia / Vaccinia virus / Proteínas Virais / Vírion / Glicoproteínas Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacínia / Vaccinia virus / Proteínas Virais / Vírion / Glicoproteínas Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos