Pascua PNQ, Jones JC, Marathe BM, Seiler P, Caufie. Baloxavir treatment delays influenza B virus transmission in ferrets and results in limited generation of drug-resistant variants. Antimicrob Agents Chemother. 2021 Aug 23:AAC011372
Clinical efficacy of the influenza antiviral baloxavir marboxil (baloxavir) is compromised by treatment-emergent variants harboring a polymerase acidic protein I38T substitution. However, the fitness of I38T-containing influenza B viruses (IBVs) remains inadequately defined. After confirming the pharmacokinetics of the compound in ferrets, animals were injected subcutaneously with 8 mg/kg of baloxavir acid (BXA) 24 h post-inoculation with recombinant BXA-sensitive (BXA-Sen, I38) or BXA-resistant (BXA-Res, I38T) B/Brisbane/60/2008 (Victoria lineage) virus. BXA treatment of donor ferrets reduced virus replication and delayed transmission of the BXA-Sen but not the BXA-Res IBV. The I38 genotype remained dominant in the BXA-Sen animals, even under BXA treatment. In competitive-mixture experiments, no transmission to aerosol-contacts was seen from BXA-treated donors coinfected with the BXA-Sen and BXA-Res B/Brisbane/60/2008 viruses. However, in parallel mixed-infections with the B/Phuket/3073/2013 (Yamagata lineage) virus background, BXA treatment failed to block airborne transmission of the BXA-Res virus and the I38T genotype generally predominated. Therefore, relative fitness of BXA-Res IBVs is complex and dependent on the virus backbone and within-host virus competition. BXA treatment of single-virus infected ferrets hampers aerosol transmission of the BXA-Sen virus and does not readily generate BXA-Res variants, while mixed-infections may result in propagation of BXA-Res IBVs of the Yamagata lineage. Our findings confirm the antiviral potency of baloxavir against IBVs while supporting optimization of the dosing regimen to maximize clinical benefit.
See Also:
Latest articles in those days:
- The evolution, complexity, and diversity of swine influenza viruses in China: A hidden public health threat 18 hours ago
- MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses 19 hours ago
- Histopathologic Features and Viral Antigen Distribution of H5N1 Highly Pathogenic Avian Influenza Virus Clade 2.3.4.4b from the 2022–2023 Outbreak in Iowa Wild Birds 19 hours ago
- Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm 23 hours ago
- Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle 23 hours ago
[Go Top] [Close Window]