Takashita Emi, Fujisaki Seiichiro, Yokoyama Masaru, Shirakura Masayuki, Morita Hiroko, Nakamura Kazuya, Kishida Noriko, Kuwahara Tomoko, Sato Hironori, Doi Ikuko, Sato Yuji, Takao Shinichi, Shimazu Yukie, Shimomura Takeshi, Ito Takuo, Watanabe Shinji, Odagiri Takato
Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Pathogens. 2020 Sep 2;9(9):725. doi: 10.3390/pathogens9090725.
Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir compared to single H275Y mutant viruses. Baloxavir could be a treatment option against the multidrug-resistant viruses because these dual H275Y mutant viruses showed susceptibility to this drug. The G147R substitution appears to stabilize the NA structure, with the fitness of the H275Y/G147R mutant virus being similar or somewhat better than that of the wild-type virus. Since the multidrug-resistant viruses may be able to transmit between humans, surveillance of these viruses must continue to improve clinical management and to protect public health.
携带双重神经氨酸酶（NA）替代的甲型H1N1pdm09流感病毒是在免疫功能低下的患者接受一种或多种NA抑制剂治疗后分离出来的。这些突变病毒的NA具有H275Y/I223R、H275Y/I223K或H275Y/G147R替代，与单一H275Y突变病毒相比，对奥司他韦和帕拉米韦的交叉耐药性增强，对扎那米韦的敏感性降低。巴洛沙韦可能是针对多重耐药病毒的一种治疗选择，因为这些双重H275Y突变病毒对该药物敏感。G147R替代似乎稳定了NA结构，H275Y/G147R突变病毒的适应性与野生型病毒相似或略好。由于多重耐药病毒可能能够在人与人之间传播，因此必须继续对这些病毒进行监测，以改善临床管理并保护公众健康。
