Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir.
J Infect Dis
; 221(3): 367-371, 2020 01 14.
Article
em En
| MEDLINE
| ID: mdl-31541547
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Oxazinas
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Piridinas
/
Tiepinas
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Triazinas
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Replicação Viral
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Infecções por Orthomyxoviridae
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Farmacorresistência Viral
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Vírus da Influenza A Subtipo H1N1
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Vírus da Influenza A Subtipo H3N2
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article