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Modulation of human-to-swine influenza a virus adaptation by the neuraminidase low-affinity calcium-binding pocket.
Cardenas, Matias; Seibert, Brittany; Cowan, Brianna; Caceres, C Joaquin; Gay, L Claire; Cargnin Faccin, Flavio; Perez, Daniel R; Baker, Amy L; Anderson, Tavis K; Rajao, Daniela S.
Afiliação
  • Cardenas M; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Seibert B; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Cowan B; W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Caceres CJ; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Gay LC; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Cargnin Faccin F; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Perez DR; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Baker AL; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Anderson TK; National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA.
  • Rajao DS; National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA.
Commun Biol ; 7(1): 1230, 2024 Oct 01.
Article em En | MEDLINE | ID: mdl-39354058
ABSTRACT
Frequent interspecies transmission of human influenza A viruses (FLUAV) to pigs contrasts with the limited subset that establishes in swine. While hemagglutinin mutations are recognized for their role in cross-species transmission, the contribution of neuraminidase remains understudied. Here, the NA's role in FLUAV adaptation was investigated using a swine-adapted H3N2 reassortant virus with human-derived HA and NA segments. Adaptation in pigs resulted in mutations in both HA (A138S) and NA (D113A). The D113A mutation abolished calcium (Ca2+) binding in the low-affinity Ca2+-binding pocket of NA, enhancing enzymatic activity and thermostability under Ca2+-depleted conditions, mirroring swine-origin FLUAV NA behavior. Structural analysis predicts that swine-adapted H3N2 viruses lack Ca2+ binding in this pocket. Further, residue 93 in NA (G93 in human, N93 in swine) also influences Ca2+ binding and impacts NA activity and thermostability, even when D113 is present. These findings demonstrate that mutations in influenza A virus surface proteins alter evolutionary trajectories following interspecies transmission and reveal distinct mechanisms modulating NA activity during FLUAV adaptation, highlighting the importance of Ca2+ binding in the low-affinity calcium-binding pocket.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cálcio / Neuraminidase Limite: Animals / Humans Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cálcio / Neuraminidase Limite: Animals / Humans Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido