H1N1 influenza A virus neuraminidase modulates infectivity in mice

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• 作者：Olivier Ferraris^a ; ^b ; ¹ ; Vanessa Escuret^a ; ^b ; ^c ; Maude Bouscambert^a ; ^b ; ^c ; Jean-Sé ; bastien Casalegno^a ; ^b ; ^c ; Fré ; dé ; ric Jacquot^d ; Hervé ; Raoul^d ; Valé ; rie Caro^e ; Martine Valette^c ; Bruno Lina^a ; ^b ; ^c ; Michè ; le Ottmann^a ; ^b ; ^{michele.ottmann@univ-lyon1.fr}
• 关键词：Influenza A virus ; Pandemic 2009 H1N1 virus ; Neuraminidase ; Oseltamivir ; Reassortant virus ; Mouse model
• 刊名：Antiviral Research
• 出版年：2012
• 期刊代码：7_01663542
• 类别：imm
• 出版时间：March, 2012
• 卷：93
• 期：3
• 页码：374-380
• 文件大小：480 K

摘要

In the 2 years since the onset of the H1N1 2009 pandemic virus (H1N1pdm09), sporadic cases of oseltamivir-resistant viruses have been reported. We investigated the impact of oseltamivir-resistant neuraminidase from H1N1 Brisbane-like (seasonal) and H1N1pdm09 viruses on viral pathogenicity in mice. Reassortant viruses with the neuraminidase from seasonal H1N1 virus were obtained by co-infection of a H1N1pdm09 virus and an oseltamivir-resistant H1N1 Brisbane-like virus. Oseltamivir-resistant H1N1pdm09 viruses were also isolated from patients. After biochemical characterization, the pathogenicity of these viruses was assessed in a murine model. We confirmed a higher infectivity, in mice, of the H1N1pdm09 virus compared to seasonal viruses. Surprisingly, the oseltamivir-resistant H1N1pdm09 virus was more infectious than its sensitive counterpart. Moreover, the association of H1N1pdm09 hemagglutinin and an oseltamivir-resistant neuraminidase improved the infectivity of reassortant viruses in mice, regardless of the NA origin: seasonal (Brisbane-like) or pandemic strain. This study highlights the need to closely monitor the emergence of oseltamivir-resistant viruses.