H1N1 influenza A virus neuraminidase modulates infectivity in mice.
In the 2years 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.
Université de Lyon, F-69000 Lyon, France.
Olivier
O
Ferraris
Vanessa
V
Escuret
Maude
M
Bouscambert
Jean-Sébastien
JS
Casalegno
Frédéric
F
Jacquot
Hervé
H
Raoul
Valérie
V
Caro
Martine
M
Valette
Bruno
B
Lina
Michèle
M
Ottmann
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D007251:Influenza, Human / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D053139:Oseltamivir / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D000998:Antiviral Agents; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase