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Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir.

ABSTRACT: Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir-resistant viruses needed for informed risk assessment.

SUBMITTER: Chesnokov A

PROVIDER: S-EPMC8851376 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir.

Chesnokov Anton A Patel Mira C MC Mishin Vasiliy P VP De La Cruz Juan A JA Lollis Lori L Nguyen Ha T HT Dugan Vivien V Wentworth David E DE Gubareva Larisa V LV

The Journal of infectious diseases 20200101 3

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, ...[more]

PMID: 31541547

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