Division of Public Health, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuoku, Niigata City, Niigata Prefecture 951-8510, Japan.
J Clin Virol. 2010 Jan;47(1):23-8. doi: 10.1016/j.jcv.2009.11.003. Epub 2009 Dec 3.
A substantial increase in oseltamivir-resistant A(H1N1) influenza viruses was reported in Europe in late 2007.
To monitor the antiviral susceptibility profile of human A(H1N1) influenza viruses in Japan during the 2007-2008 and 2008-2009 seasons.
Viruses were obtained from respiratory samples of patients with influenza collected in Japan between December 2007 and April 2008 (n=1046) and between December 2008 and April 2009 (n=1789). Oseltamivir resistance was determined by an H274Y-specific real-time PCR cycling probe assay and a neuraminidase inhibition assay. Amantadine resistance was assessed by sequencing the M2 gene. Sequencing of the hemagglutinin and NA genes was performed to infer phylogenetic relationships between different strains.
Three of 687 (0.4%) A(H1N1) viruses from the 2007-2008 season and 745 of 745 (100%) viruses from the 2008-2009 season carried the NA-H274Y substitution and demonstrated a >300-fold reduction in oseltamivir susceptibility. All oseltamivir-resistant viruses from the 2008-2009 season possessed an A193T substitution in the receptor-binding domain of the hemagglutinin. Amantadine resistance was detected in 431 of 687 (62.7%) and 0 of 745 (0.0%) of the A(H1N1) viruses from the 2007-2008 and 2008-2009 seasons, respectively.
A dramatic surge in oseltamivir-resistant A(H1N1) viruses possessing the NA-H274Y substitution was detected in Japan during the 2008-2009 season. The emergence of oseltamivir-resistant viruses was facilitated by mutations in the viral genome. Intensified surveillance, including phenotypic assays and sequencing of the hemagglutinin, neuraminidase, and M2 gene would allow monitoring of the spread and evolution of drug-resistant influenza virus variants.
2007 年末，欧洲报告了大量奥司他韦耐药的 A(H1N1)流感病毒。
监测 2007-2008 年和 2008-2009 年日本人群中甲型 H1N1 流感病毒的抗病毒敏感性特征。
从 2007 年 12 月至 2008 年 4 月（n=1046）和 2008 年 12 月至 2009 年 4 月（n=1789）日本流感患者的呼吸道样本中获得病毒。通过针对 H274Y 的实时 PCR 循环探针测定和神经氨酸酶抑制测定来确定奥司他韦耐药性。通过测序 M2 基因来评估金刚烷胺耐药性。对血凝素和 NA 基因进行测序以推断不同菌株之间的系统发育关系。
2007-2008 年季节的 687 株（0.4%）A(H1N1)病毒中有 3 株和 2008-2009 年季节的 745 株（100%）病毒均携带 NA-H274Y 取代，其对奥司他韦的敏感性降低了>300 倍。2008-2009 年季节的所有奥司他韦耐药病毒均在血凝素的受体结合域中具有 A193T 取代。2007-2008 年和 2008-2009 年季节的 A(H1N1)病毒中，分别有 687 株（62.7%）和 745 株（0.0%）检测到金刚烷胺耐药。
2008-2009 年日本季节性流感中发现了大量具有 NA-H274Y 取代的奥司他韦耐药 A(H1N1)病毒。病毒基因组中的突变促进了奥司他韦耐药病毒的出现。加强监测，包括表型检测和血凝素、神经氨酸酶和 M2 基因的测序，将有助于监测耐药流感病毒变异株的传播和演变。
