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Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse.
J Gen Virol. 2019 11; 100(11):1471-1477.JG

Abstract

Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease of the influenza virus polymerase acidic protein (PA), exerts an antiviral effect against influenza A virus. It has been available in Japan since March 2018. This study evaluated the antiviral efficacy of BXM against equine influenza A virus (EIV) by an experimental challenge study using horses. Six horses were experimentally inoculated with EIV, and BXM was administered to the three horses at 2 days post inoculation. Horses treated with BXM showed milder clinical signs than horses without treatment and shed less virus. These results suggest that BXM is effective against EIV. The PA gene of viruses present in the nasopharyngeal swabs collected from horses treated with BXM was sequenced. Two mutations have been detected in viruses recovered from horses treated with BXM. These mutations were the substitution of isoleucine with threonine at position 38 (PA-I38T) and that of asparagine with aspartic acid at position 675 in PA (PA-N675D). A mutated virus with PA-I38T was less susceptible to BXM than viruses with PA-N675D or without mutation. A PA-I38T mutation has also been detected in viruses recovered from humans treated with BXM and is responsible for the reduction in susceptibility to BXM. This suggests that we should not unthinkingly use BXM for the treatment of EI. BXM is likely to easily induce resistance in influenza A viruses, not only in humans but also in horses.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Equine Research Institute, Japan Racing Association, Shimotsuke, Tochigi, Japan.

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31526451

Citation

Nemoto, Manabu, et al. "Mutated Influenza a Virus Exhibiting Reduced Susceptibility to Baloxavir Marboxil From an Experimentally Infected Horse." The Journal of General Virology, vol. 100, no. 11, 2019, pp. 1471-1477.

Nemoto M, Tamura N, Bannai H, et al. Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse. J Gen Virol. 2019;100(11):1471-1477.

Nemoto, M., Tamura, N., Bannai, H., Tsujimura, K., Kokado, H., Ohta, M., & Yamanaka, T. (2019). Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse. The Journal of General Virology, 100(11), 1471-1477. https://doi.org/10.1099/jgv.0.001325

Nemoto M, et al. Mutated Influenza a Virus Exhibiting Reduced Susceptibility to Baloxavir Marboxil From an Experimentally Infected Horse. J Gen Virol. 2019;100(11):1471-1477. PubMed PMID: 31526451.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse. AU - Nemoto,Manabu, AU - Tamura,Norihisa, AU - Bannai,Hiroshi, AU - Tsujimura,Koji, AU - Kokado,Hiroshi, AU - Ohta,Minoru, AU - Yamanaka,Takashi, PY - 2019/9/19/pubmed PY - 2020/6/10/medline PY - 2019/9/19/entrez KW - PA-I38T KW - baloxavir marboxil KW - equine influenza virus KW - influenza A virus KW - mutation SP - 1471 EP - 1477 JF - The Journal of general virology JO - J Gen Virol VL - 100 IS - 11 N2 - Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease of the influenza virus polymerase acidic protein (PA), exerts an antiviral effect against influenza A virus. It has been available in Japan since March 2018. This study evaluated the antiviral efficacy of BXM against equine influenza A virus (EIV) by an experimental challenge study using horses. Six horses were experimentally inoculated with EIV, and BXM was administered to the three horses at 2 days post inoculation. Horses treated with BXM showed milder clinical signs than horses without treatment and shed less virus. These results suggest that BXM is effective against EIV. The PA gene of viruses present in the nasopharyngeal swabs collected from horses treated with BXM was sequenced. Two mutations have been detected in viruses recovered from horses treated with BXM. These mutations were the substitution of isoleucine with threonine at position 38 (PA-I38T) and that of asparagine with aspartic acid at position 675 in PA (PA-N675D). A mutated virus with PA-I38T was less susceptible to BXM than viruses with PA-N675D or without mutation. A PA-I38T mutation has also been detected in viruses recovered from humans treated with BXM and is responsible for the reduction in susceptibility to BXM. This suggests that we should not unthinkingly use BXM for the treatment of EI. BXM is likely to easily induce resistance in influenza A viruses, not only in humans but also in horses. SN - 1465-2099 UR - https://www.unboundmedicine.com/medline/citation/31526451/Mutated_influenza_A_virus_exhibiting_reduced_susceptibility_to_baloxavir_marboxil_from_an_experimentally_infected_horse_ DB - PRIME DP - Unbound Medicine ER -