Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31541547.
- Also identified by DOI 10.1093/infdis/jiz472 and PMC identifier 8851376.
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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.
Medical subject headings
- Antiviral Agents
- Drug Resistance, Viral
- Influenza A Virus, H1N1 Subtype
- Influenza A Virus, H3N2 Subtype
- Orthomyxoviridae Infections
- Oxazines
- Pyridines
- Thiepins
- Triazines
- Virus Replication