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Oseltamivir Expands Quasispecies of Influenza Virus through Cell-to-cell Transmission

tetano

Editor, Senior Moderator
Sci Rep. 2015 Mar 16;5:9163. doi: 10.1038/srep09163.
[h=1]Oseltamivir Expands Quasispecies of Influenza Virus through Cell-to-cell Transmission.[/h] Mori K[SUP]1[/SUP], Murano K[SUP]1[/SUP], Ohniwa RL[SUP]2[/SUP], Kawaguchi A[SUP]1[/SUP], Nagata K[SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The population of influenza virus consists of a huge variety of variants, called quasispecies, due to error-prone replication. Previously, we reported that progeny virions of influenza virus become infected to adjacent cells via cell-to-cell transmission pathway in the presence of oseltamivir. During cell-to-cell transmission, viruses become infected to adjacent cells at high multiplicity since progeny virions are enriched on plasma membrane between infected cells and their adjacent cells. Co-infection with viral variants may rescue recessive mutations with each other. Thus, it is assumed that the cell-to-cell transmission causes expansion of virus quasispecies. Here, we have demonstrated that temperature-sensitive mutations remain in progeny viruses even at non-permissive temperature by co-infection in the presence of oseltamivir. This is possibly due to a multiplex infection through the cell-to-cell transmission by the addition of oseltamivir. Further, by the addition of oseltamivir, the number of missense mutation introduced by error-prone replication in segment 8 encoding NS1 was increased in a passage-dependent manner. The number of missense mutation in segment 5 encoding NP was not changed significantly, whereas silent mutation was increased. Taken together, we propose that oseltamivir expands influenza virus quasispecies via cell-to-cell transmission, and may facilitate the viral evolution and adaptation.


PMID: 25772381 [PubMed - in process]
 
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