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为了解我国大陆流行的季节性流感病毒对抗流感病毒药物的敏感性，本文对2023-2024流感监测年度分离的季节性流感病毒进行了神经氨酸酶抑制剂和巴洛沙韦的耐药检测。基于表型方法检测的5 341株季节性流感毒株中，9株A(H1N1)pdm09亚型对Oseltamivir敏感高度降低，NA基因上有H275Y位点的变异；2株B/Victoria系对Oseltamivir和Zanamivir敏感性均降低，NA基因上分别有I348T和D197N位点的变异。基于基因型方法检测的1 207株季节性流感毒株中，1株A(H1N1)pdm09亚型在PA基因上有K34R和E198K位点的变异，2株A(H3N2)亚型在PA基因上有L28P位点的变异，提示对巴洛沙韦的敏感性降低。因此，上述监测数据表明2023-2024年我国大陆流行的季节性流感病毒总体上对神经氨酸酶抑制剂和巴洛沙韦敏感，这两类药物依然是治疗流感病毒感染的适当选择，而密切监测病毒对抗病毒药物的敏感性是必要的。
Abstract：To evaluate the susceptibility of seasonal influenza viruses circulating in mainland of China to antiviral drugs, this study tested seasonal influenza viruses isolated during the 2023-2024 influenza season for resistance to neuraminidase inhibitors and Baloxavir. Of the 5,341 seasonal influenza strains analyzed using phenotypic methods, nine A(H1N1)pdm09 strains exhibited highly reduced susceptibility to Oseltamivir, all carrying the NA-H275Y amino acid substitution. Additionally, two B/Victoria lineage strains showed reduced susceptibility to both Oseltamivir and Zanamivir, with NA-I348T or NA-D197N substitutions, respectively. Of the 1,207seasonal influenza viruses assessed through genotypic analysis, one A(H1N1)pdm09 strain had dual PA-K34R and PA-E198K substitutions, and two A(H3N2) strains carried a PA-L28P substitution, indicating potential reduced susceptibility to Baloxavir. Overall, the findings suggest that seasonal influenza viruses circulating in mainland of China during the 2023-2024 influenza season remain generally sensitive to neuraminidase inhibitors and Baloxavir, making these drugs suitable options for treating influenza infections. However, continued surveillance of antiviral susceptibility is essential.
[1]中国医师协会急诊医师分会，中华医学会急诊医学分会，中国急诊专科医联体，等.成人流行性感冒诊疗规范急诊专家共识（2022版）[J].中华急诊医学杂志，2023, 32(1):17-31. DOI:10. 3760/cma. j. issn. 1671-0282. 2023. 01. 005.
[2] Takashita E, Daniels RS, Fujisaki S, et al. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017–2018[J].Antiviral Res, 2020, 175:104718. DOI:10. 1016/j.antiviral. 2020. 104718.
[3] Govorkova EA, Takashita E, Daniels RS, et al. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020[J].Antiviral Res, 2022, 200:105281. DOI:10. 1016/j.antiviral. 2022. 105281.
[4] Hurt AC, Chotpitayasunondh T, Cox NJ, et al.Antiviral resistance during the 2009 influenza A H1N1pandemic:public health, laboratory, and clinical perspectives[J]. Lancet Infect Dis, 2012, 12(3):240-248. DOI:10. 1016/S1473-3099(11)70318-8.
[5] Li TC, Chan MC, Lee N. Clinical implications of antiviral resistance in influenza[J]. Viruses, 2015, 7(9):4929-4944. DOI:10. 3390/v7092850.
[6] Gubareva LV, Besselaar TG, Daniels RS, et al.Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2015–2016[J].Antiviral Res, 2017, 146:12-20. DOI:10. 1016/j.antiviral. 2017. 08. 004.
[7] Kelso A, Hurt AC. The ongoing battle against influenza:drug-resistant influenza viruses:why fitness matters[J]. Nat Med, 2012, 18(10):1470-1471.DOI:10. 1038/nm. 2954.
[8] Butler J, Hooper KA, Petrie S, et al. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses[J]. PLoS Pathog, 2014, 10(4):e1004065. DOI:10. 1371/journal. ppat. 1004065.
[9] Huang W, Cheng Y, Li X, et al. Neuraminidase inhibitor susceptibility profile of human influenza viruses during the 2016–2017 influenza season in Mainland China[J]. J Infect Chemother, 2018, 24(9):729-733.DOI:10. 1016/j. jiac. 2018. 05. 003.
[10]Mohan T, Nguyen HT, Kniss K, et al. Cluster of oseltamivir-resistant and hemagglutinin antigenically drifted influenza A(H1N1)pdm09 viruses, texas, USA,January 2020[J]. Emerg Infect Dis, 2021, 27(7):1953-1957. DOI:10. 3201/eid2707. 204593.
[11]Leung RC, Ip JD, Chen LL, et al. Global emergence of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses with I223V and S247N mutations:implications for antiviral resistance monitoring[J].Lancet Microbe, 2024, 5(7):627-628. DOI:10. 1016/s2666-5247(24)00037-5.
[12]Patel MC, Nguyen HT, Pascua PNQ, et al.Multicountry spread of influenza A(H1N1)pdm09viruses with reduced oseltamivir inhibition, May 2023-February 2024[J]. Emerg Infect Dis, 2024, 30(7):1410-1415. DOI:10. 3201/eid3007. 240480.
[13]Brown SK, Tseng YY, Aziz A, et al. Characterization of influenza B viruses with reduced susceptibility to influenza neuraminidase inhibitors[J]. Antiviral Res,2022, 200:105280. DOI:10. 1016/j.antiviral. 2022. 105280.
[14]Fujisaki S, Takashita E, Yokoyama M, et al. A single E105K mutation far from the active site of influenza B virus neuraminidase contributes to reduced susceptibility to multiple neuraminidase-inhibitor drugs[J]. Biochem Biophys Res Commun, 2012, 429(1-2):51-56. DOI:10. 1016/j. bbrc. 2012. 10. 095.
[15]Sheu TG, Deyde VM, Okomo-Adhiambo M, et al.Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008[J]. Antimicrob Agents Chemother, 2008, 52(9):3284-3292. DOI:10. 1128/AAC. 00555-08.
[16]Gubareva LV, Mishin VP, Patel MC, et al. Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18seasons[J]. Euro Surveill, 2019, 24(3):1800666.DOI:10. 2807/1560-7917. ES. 2019. 24. 3. 1800666.
[17]Hirotsu N, Sakaguchi H, Sato C, et al. Baloxavir marboxil in Japanese pediatric patients with influenza:safety and clinical and virologic outcomes[J]. Clin Infect Dis, 2020, 71(4):971-981. DOI:10. 1093/cid/ciz908.
[18]Uehara T, Hayden FG, Kawaguchi K, et al. Treatment-emergent influenza variant viruses with reduced baloxavir susceptibility:impact on clinical and virologic outcomes in uncomplicated influenza[J]. J Infect Dis,2020, 221(3):346-355. DOI:10. 1093/infdis/jiz244.
[19]Imai M, Yamashita M, Sakai-Tagawa Y, et al.Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets[J]. Nat Microbiol, 2020, 5(1):27-33. DOI:10. 1038/s41564-019-0609-0.
[20]Omoto S, Speranzini V, Hashimoto T, et al.Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil[J]. Sci Rep, 2018, 8(1):9633. DOI:10. 1038/s41598-018-27890-4.
[21]Takizawa N, Momose F. A novel E198K substitution in the PA gene of influenza A virus with reduced susceptibility to baloxavir acid[J]. Arch Virol, 2022,167(7):1565-1570. DOI:10. 1007/s00705-022-05456-0.
[22]中国疾病预防控制中心.中国流感监测周报[EB/OL].(2024-04-07)[2024-09-10]. https：//ivdc.chinacdc. cn/cnic/en/.
[23]成艳辉，刘佳，谭敏菊，等. 2017—2018监测年度中国大陆A(H1N1)pdm09亚型流感病毒抗原性和基因特性分析[J].病毒学报，2019, 35(3):431-439. DOI:10. 13242/j. cnki. bingduxuebao. 003543.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004616
中图分类号:R511.7;R181.3
引用信息:
[1]隗合江,李希妍,成艳辉等.2023-2024流感监测年度中国大陆流行的季节性流感病毒对神经氨酸酶抑制剂和巴洛沙韦的敏感性[J].病毒学报,2024,40(06):1255-1262.DOI:10.13242/j.cnki.bingduxuebao.004616.
基金信息:
国家重点研发计划（项目号：2022YFF1203201）,题目：病毒变异演化预测与预警技术基础体系建立~~