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Structural homology screens reveal host-derived poxvirus protein families impacting inflammasome activity.
Boys, Ian N; Johnson, Alex G; Quinlan, Meghan R; Kranzusch, Philip J; Elde, Nels C.
Afiliação
  • Boys IN; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Johnson AG; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Quinlan MR; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Kranzusch PJ; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Elde NC; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: nelde@genetics.utah.edu.
Cell Rep ; 42(8): 112878, 2023 08 29.
Article em En | MEDLINE | ID: mdl-37494187
ABSTRACT
Viruses acquire host genes via horizontal transfer and can express them to manipulate host biology during infections. Some homologs retain sequence identity, but evolutionary divergence can obscure host origins. We use structural modeling to compare vaccinia virus proteins with metazoan proteomes. We identify vaccinia A47L as a homolog of gasdermins, the executioners of pyroptosis. An X-ray crystal structure of A47 confirms this homology, and cell-based assays reveal that A47 interferes with caspase function. We also identify vaccinia C1L as the product of a cryptic gene fusion event coupling a Bcl-2-related fold with a pyrin domain. C1 associates with components of the inflammasome, a cytosolic innate immune sensor involved in pyroptosis, yet paradoxically enhances inflammasome activity, suggesting differential modulation during infections. Our findings demonstrate the increasing power of structural homology screens to reveal proteins with unique combinations of domains that viruses capture from host genes and combine in unique ways.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Poxviridae / Vacínia / Vírus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Poxviridae / Vacínia / Vírus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
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