H1N1 influenza A virus neuraminidase modulates infectivity in mice

作者：Ferraris Olivier; Escuret Vanessa; Bouscambert Maude; Casalegno Jean Sebastien; Jacquot Frederic; Raoul Herve; Caro Valerie; Valette Martine; Lina Bruno; Ottmann Michele^*

来源：Antiviral Research, 2012, 93(3): 374-380.

DOI：10.1016/j.antiviral.2012.01.008

• Influenza A virus
• Pandemic 2009 H1N1 virus
• Neuraminidase
• Oseltamivir
• Reassortant virus
• Mouse model

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.

• 出版日期2012-3