Scientific paper 49 – An oseltamivir treatment-selected influenza A/N2 virus with a R292K mutation in the neuraminidase gene has reduced infectivity in vivo

March 7, 2017 3:16 pm

An oseltamivir treatment-selected influenza A/N2 virus with a R292K mutation in the neuraminidase gene has reduced infectivity in vivo

Journal of  Clinical Virology, 2000, Volume 18, p 251 -269

Authors: J Ives, J Carr, N A Roberts, C Y Tai, D B Mendel, L Kelly, R Lambkin-Williams, J S Oxford

Abstract

An influenza A/N2 virus carrying the R292K mutation in the neuraminidase gene has been isolated from a patient on an oseltamivir treatment study. Clinically derived R292K neuraminidase has a two-fold reduction in affinity for (synthetic) substrate, and a great then 9000-fold reduction in sensitivity to inhibition by Ro 64-0802 (GS4071). The R292K neuraminidase does not impart advantage to the mutant virus in terms of replication in MDCK cells. The infectivity and replicative ability of R292K mutant virus was reduced by at least 100-fold in a mouse model of influenza infection. In the ferret model of influenza infection, the infectivity of the mutant virus was reduced by at least 100-fold and its replicative ability was reduced by at least 10,000-fold. Pathogenicity of R292K neuraminidase virus was reduced in parallel with virus titres in ferrets. The compromised infectivity and pathogenicity demonstrated in vivo indicate that virus carrying R292K mutation in the neuraminidase gene is likely to have a reduced risk of transmission in man.

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