Emergence of Oseltamivir-Resistant H7N9 Influenza Viruses in Immunosuppressed Cynomolgus Macaques.

Maki Kiso; Kiyoko Iwatsuki-Horimoto; Seiya Yamayoshi; Ryuta Uraki; Mutsumi Ito; Noriko Nakajima; Shinya Yamada; Masaki Imai; Eiryo Kawakami; Yuriko Tomita; Satoshi Fukuyama; Yasushi Itoh; Kazumasa Ogasawara; Lopes, Tiago J. S.; Tokiko Watanabe; Moncla, Louise H.; Hideki Hasegawa; Friedrich, Thomas C.; Neumann, Gabriele; Yoshihiro Kawaoka

Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir. Disease severity and mortality were higher in immunosuppressed than in immunocompetent animals. Oseltamivir treatment at 2 different doses reduced A(H7N9) viral titers in infected animals, but even high-dose oseltamivir did not block viral replication sufficiently to suppress the emergence of resistant variants. Some resistant variants were not appreciably attenuated in cultured cells, but an oseltamivir-resistant A(H7N9) virus did not transmit among ferrets. These findings are useful for the control of A(H7N9) virus infections in clinical settings.

OSELTAMIVIR; INFLUENZA; VIRUSES; MACAQUES; VIROCAP (Medical test)

Journal of Infectious Diseases, 2017, Vol 216, Issue 5, p582

0022-1899

Academic Journal

10.1093/infdis/jix296