1887

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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001325
2019-11-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/100/11/1471.html?itemId=/content/journal/jgv/10.1099/jgv.0.001325&mimeType=html&fmt=ahah

References

  1. Singh RK, Dhama K, Karthik K, Khandia R, Munjal A et al. A comprehensive review on equine influenza virus: etiology, epidemiology, pathobiology, advances in developing diagnostics, vaccines, and control strategies. Front Microbiol 2018; 9:9 [View Article]
    [Google Scholar]
  2. Yamanaka T, Niwa H, Tsujimura K, Kondo T, Matsumura T. Epidemic of equine influenza among vaccinated racehorses in Japan in 2007. J Vet Med Sci 2008; 70:623–625 [View Article]
    [Google Scholar]
  3. Rees WA, Harkins JD, Lu M, Holland RE, Lehner AF et al. Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2. Am J Vet Res 1999; 60:888–894
    [Google Scholar]
  4. Yamanaka T, Tsujimura K, Kondo T, Hobo S, Matsumura T. Efficacy of oseltamivir phosphate to horses inoculated with equine influenza A virus. J Vet Med Sci 2006; 68:923–928 [View Article]
    [Google Scholar]
  5. Yamanaka T, Bannai H, Nemoto M, Tsujimura K, Kondo T et al. Efficacy of a single intravenous dose of the neuraminidase inhibitor peramivir in the treatment of equine influenza. Vet J 2012; 193:358–362 [View Article]
    [Google Scholar]
  6. Koszalka P, Tilmanis D, Hurt AC. Influenza antivirals currently in late-phase clinical trial. Influenza Other Respir Viruses 2017; 11:240–246 [View Article]
    [Google Scholar]
  7. Takashita E, Kawakami C, Ogawa R, Morita H, Fujisaki S et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill 2019; 24:pii=1900170 [View Article]
    [Google Scholar]
  8. Taniguchi K, Ando Y, Nobori H, Toba S, Noshi T et al. Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Sci Rep 2019; 9:3466 [View Article]
    [Google Scholar]
  9. Koszalka P, Tilmanis D, Roe M, Vijaykrishna D, Hurt AC. Baloxavir marboxil susceptibility of influenza viruses from the Asia-Pacific, 2012-2018. Antiviral Res 2019; 164:91–96 [View Article]
    [Google Scholar]
  10. Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res 2018; 160:109–117 [View Article]
    [Google Scholar]
  11. Omoto S, Speranzini V, Hashimoto T, Noshi T, Yamaguchi H et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep 2018; 8:9633 [View Article]
    [Google Scholar]
  12. Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD et al. Baloxavir Marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018; 379:913–923 [View Article]
    [Google Scholar]
  13. Takashita E, Kawakami C, Morita H, Ogawa R, Fujisaki S et al. Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill 2019; 24:pii=1800698 [View Article]
    [Google Scholar]
  14. Witkowska-Piłaszewicz OD, Żmigrodzka M, Winnicka A, Miśkiewicz A, Strzelec K et al. Serum amyloid A in equine health and disease. Equine Vet J 2019; 51:293–298 [View Article]
    [Google Scholar]
  15. Aoki FY, Boivin G, Roberts N. Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther 2007; 12:603–616
    [Google Scholar]
  16. Rivailler P, Perry IA, Jang Y, Davis CT, Chen L-M et al. Evolution of canine and equine influenza (H3N8) viruses co-circulating between 2005 and 2008. Virology 2010; 408:71–79 [View Article]
    [Google Scholar]
  17. Yamanaka T, Cullinane A, Gildea S, Bannai H, Nemoto M et al. The potential impact of a single amino-acid substitution on the efficacy of equine influenza vaccines. Equine Vet J 2015; 47:456–462 [View Article]
    [Google Scholar]
  18. Yamanaka T, Tsujimura K, Kondo T, Matsumura T, Ishida H et al. Infectivity and pathogenicity of canine H3N8 influenza A virus in horses. Influenza Other Respir Viruses 2010; 4:345–351 [View Article]
    [Google Scholar]
  19. Yamanaka T, Nemoto M, Bannai H, Tsujimura K, Kondo T et al. Evaluation of twenty-two rapid antigen detection tests in the diagnosis of equine influenza caused by viruses of H3N8 subtype. Influenza Other Respir Viruses 2016; 10:127–133 [View Article]
    [Google Scholar]
  20. Yamanaka T, Nemoto M, Tsujimura K, Kondo T, Matsumura T. Interspecies transmission of equine influenza virus (H3N8) to dogs by close contact with experimentally infected horses. Vet Microbiol 2009; 139:351–355 [View Article]
    [Google Scholar]
  21. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938; 27:493–497
    [Google Scholar]
  22. Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR. Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 2001; 146:2275–2289 [View Article]
    [Google Scholar]
  23. Nemoto M, Yamanaka T, Bannai H, Tsujimura K, Kokado H. Complete genomic sequences of H3N8 equine influenza virus strains used as vaccine strains in Japan. Genome Announc 2018; 6:e00172–18 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001325
Loading
/content/journal/jgv/10.1099/jgv.0.001325
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error