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Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.
Siegers, Jurre Y; Ferreri, Lucas; Eggink, Dirk; Veldhuis Kroeze, Edwin J B; Te Velthuis, Aartjan J W; van de Bildt, Marco; Leijten, Lonneke; van Run, Peter; de Meulder, Dennis; Bestebroer, Theo; Richard, Mathilde; Kuiken, Thijs; Lowen, Anice C; Herfst, Sander; van Riel, Debby.
Afiliación
  • Siegers JY; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Ferreri L; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Eggink D; Department of Medical Microbiology, Amsterdam UMC, Amsterdam, The Netherlands.
  • Veldhuis Kroeze EJB; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Te Velthuis AJW; Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
  • van de Bildt M; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Leijten L; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • van Run P; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • de Meulder D; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Bestebroer T; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Richard M; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Kuiken T; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Lowen AC; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Herfst S; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • van Riel D; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
PLoS Pathog ; 19(3): e1011214, 2023 03.
Article en En | MEDLINE | ID: mdl-36897923
Central nervous system (CNS) disease is the most common extra-respiratory tract complication of influenza A virus infections in humans. Remarkably, zoonotic highly pathogenic avian influenza (HPAI) H5N1 virus infections are more often associated with CNS disease than infections with seasonal influenza viruses. Evolution of avian influenza viruses has been extensively studied in the context of respiratory infections, but evolutionary processes in CNS infections remain poorly understood. We have previously observed that the ability of HPAI A/Indonesia/5/2005 (H5N1) virus to replicate in and spread throughout the CNS varies widely between individual ferrets. Based on these observations, we sought to understand the impact of entrance into and replication within the CNS on the evolutionary dynamics of virus populations. First, we identified and characterized three substitutions-PB1 E177G and A652T and NP I119M - detected in the CNS of a ferret infected with influenza A/Indonesia/5/2005 (H5N1) virus that developed a severe meningo-encephalitis. We found that some of these substitutions, individually or collectively, resulted in increased polymerase activity in vitro. Nevertheless, in vivo, the virus bearing the CNS-associated mutations retained its capacity to infect the CNS but showed reduced dispersion to other anatomical sites. Analyses of viral diversity in the nasal turbinate and olfactory bulb revealed the lack of a genetic bottleneck acting on virus populations accessing the CNS via this route. Furthermore, virus populations bearing the CNS-associated mutations showed signs of positive selection in the brainstem. These features of dispersion to the CNS are consistent with the action of selective processes, underlining the potential for H5N1 viruses to adapt to the CNS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Infecciones por Orthomyxoviridae / Gripe Humana / Subtipo H5N1 del Virus de la Influenza A / Gripe Aviar Límite: Animals / Humans Idioma: En Revista: PLoS Pathog Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus de la Influenza A / Infecciones por Orthomyxoviridae / Gripe Humana / Subtipo H5N1 del Virus de la Influenza A / Gripe Aviar Límite: Animals / Humans Idioma: En Revista: PLoS Pathog Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos