ArticlePLoS pathogens2021
Evaluating the fitness of PA/I38T-substituted influenza A viruses with reduced baloxavir susceptibility in a competitive mixtures ferret model.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 34 citations in OpenAlex.
- Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.Microbiology spectrum · 2026Article
- A Structural View of Influenza Virus Ribonucleoprotein Complex and Its Functions.Microorganisms · 2026Review
- Impaired host shutoff is a fitness cost associated with baloxavir marboxil resistance mutations in influenza A virus PA/PA-X nuclease domain.PLoS pathogens · 2026Article
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- Presence of Microorganisms in the Environment: One Health Approach.Microorganisms · 2025Review
- Modeling Influenza Antiviral Strategies: Reducing Burden and Preventing Resistance.The Journal of infectious diseases · 2025Article
- PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025Review
- Genotypic and phenotypic susceptibility of emerging avian influenza A viruses to neuraminidase and cap-dependent endonuclease inhibitors.Antiviral research · 2024Article
- Article
- Structural Studies of Inhibitors with Clinically Relevant Influenza Endonuclease Variants.Biochemistry · 2024Article
- The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir.Archives of virology · 2024Article
- Genome characterization of influenza A and B viruses in New South Wales, Australia, in 2019: A retrospective study using high-throughput whole genome sequencing.Influenza and other respiratory viruses · 2024Article
- Impact of Baloxavir Resistance-Associated Substitutions on Influenza Virus Growth and Drug Susceptibility.Journal of virology · 2023Article
- Accelerating antiviral drug discovery: lessons from COVID-19.Nature reviews. Drug discovery · 2023Review
- In Vivo Antiviral Activity of Baloxavir against PA/I38T-Substituted Influenza A Viruses at Clinically Relevant Doses.Viruses · 2023Article
- Viral Fitness of Baloxavir-Resistant Recombinant Influenza B/Victoria- and B/Yamagata-like Viruses Harboring the I38T PA Change, In Vitro, Ex Vivo and in Guinea Pigs.Microorganisms · 2023Article
- Observational
- Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells.PLoS pathogens · 2023Article
- Investigating the transmission of baloxavir-resistant influenza viruses from treated index patients to untreated household contacts in the BLOCKSTONE study.Influenza and other respiratory viruses · 2023Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Baloxavir is approved in several countries for the treatment of uncomplicated influenza in otherwise-healthy and high-risk patients. Treatment-emergent viruses with reduced susceptibility to baloxavir have been detected in clinical trials, but the likelihood of widespread occurrence depends on replication capacity and onward transmission. We evaluated the fitness of A/H3N2 and A/H1N1pdm09 viruses with the polymerase acidic (PA) I38T-variant conferring reduced susceptibility to baloxavir relative to wild-type (WT) viruses, using a competitive mixture ferret model, recombinant viruses and patient-derived virus isolates. The A/H3N2 PA/I38T virus showed a reduction in within-host fitness but comparable between-host fitness to the WT virus, while the A/H1N1pdm09 PA/I38T virus had broadly similar within-host fitness but substantially lower between-host fitness. Although PA/I38T viruses replicate and transmit between ferrets, our data suggest that viruses with this amino acid substitution have lower fitness relative to WT and this relative fitness cost was greater in A/H1N1pdm09 viruses than in A/H3N2 viruses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.