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Emergence of Oseltamivir-Resistant H7N9 Influenza Viruses in Immunosuppressed Cynomolgus Macaques.
Kiso, Maki; Iwatsuki-Horimoto, Kiyoko; Yamayoshi, Seiya; Uraki, Ryuta; Ito, Mutsumi; Nakajima, Noriko; Yamada, Shinya; Imai, Masaki; Kawakami, Eiryo; Tomita, Yuriko; Fukuyama, Satoshi; Itoh, Yasushi; Ogasawara, Kazumasa; Lopes, Tiago J S; Watanabe, Tokiko; Moncla, Louise H; Hasegawa, Hideki; Friedrich, Thomas C; Neumann, Gabriele; Kawaoka, Yoshihiro.
Afiliación
  • Kiso M; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Iwatsuki-Horimoto K; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Yamayoshi S; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Uraki R; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Ito M; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Nakajima N; Department of Pathology, National Institute of Infectious Diseases, Tokyo.
  • Yamada S; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Imai M; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Kawakami E; Laboratory for Disease Systems Modeling, RIKEN Center for Integrative Medical Sciences, Kanagawa.
  • Tomita Y; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Fukuyama S; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Itoh Y; ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama.
  • Ogasawara K; Department of Pathology, Shiga University of Medical Science, Japan.
  • Lopes TJS; Department of Pathology, Shiga University of Medical Science, Japan.
  • Watanabe T; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Moncla LH; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
  • Hasegawa H; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
  • Friedrich TC; ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama.
  • Neumann G; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
  • Kawaoka Y; Wisconsin National Primate Research Center, Madison.
J Infect Dis ; 216(5): 582-593, 2017 09 01.
Article en En | MEDLINE | ID: mdl-28931216
ABSTRACT
Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir. Disease severity and mortality were higher in immunosuppressed than in immunocompetent animals. Oseltamivir treatment at 2 different doses reduced A(H7N9) viral titers in infected animals, but even high-dose oseltamivir did not block viral replication sufficiently to suppress the emergence of resistant variants. Some resistant variants were not appreciably attenuated in cultured cells, but an oseltamivir-resistant A(H7N9) virus did not transmit among ferrets. These findings are useful for the control of A(H7N9) virus infections in clinical settings.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Huésped Inmunocomprometido / Infecciones por Orthomyxoviridae / Farmacorresistencia Viral Múltiple / Oseltamivir / Subtipo H7N9 del Virus de la Influenza A / Macaca fascicularis Límite: Animals Idioma: En Revista: J Infect Dis Año: 2017 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Huésped Inmunocomprometido / Infecciones por Orthomyxoviridae / Farmacorresistencia Viral Múltiple / Oseltamivir / Subtipo H7N9 del Virus de la Influenza A / Macaca fascicularis Límite: Animals Idioma: En Revista: J Infect Dis Año: 2017 Tipo del documento: Article