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

Kotaro Mori, Kensaku Murano, Ryosuke L. Ohniwa, Atsushi Kawaguchi, Kyosuke Nagata

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number9163
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015 Mar 16
Externally publishedYes

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Oseltamivir
Orthomyxoviridae
Missense Mutation
Viruses
Coinfection
Virion
Mutation
Temperature

ASJC Scopus subject areas

  • General

Cite this

Oseltamivir Expands Quasispecies of Influenza Virus through Cell-to-cell Transmission. / Mori, Kotaro; Murano, Kensaku; Ohniwa, Ryosuke L.; Kawaguchi, Atsushi; Nagata, Kyosuke.

In: Scientific Reports, Vol. 5, 9163, 16.03.2015.

Research output: Contribution to journalArticle

Mori, Kotaro ; Murano, Kensaku ; Ohniwa, Ryosuke L. ; Kawaguchi, Atsushi ; Nagata, Kyosuke. / Oseltamivir Expands Quasispecies of Influenza Virus through Cell-to-cell Transmission. In: Scientific Reports. 2015 ; Vol. 5.
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