2018-2019年流感流行季节河北省流感病毒对神经氨酸酶抑制剂药物的耐药性研究

姜彩肖; 韩光跃; 李岩; 刘艳芳; 刘兰芬; 齐顺祥

doi:10.16462/j.cnki.zhjbkz.2020.02.021

2018-2019年流感流行季节河北省流感病毒对神经氨酸酶抑制剂药物的耐药性研究

doi: 10.16462/j.cnki.zhjbkz.2020.02.021

050021 石家庄, 河北省疾病预防控制中心病毒病防治所

基金项目: 2019年度河北省医学科学研究课题计划(20190142)

详细信息

通讯作者:
齐顺祥, E-mail:hbcdc999@126.com

中图分类号: R181.1
计量
- 文章访问数: 353
- HTML全文浏览量: 156
- PDF下载量: 24
- 被引次数: 0
出版历程
- 收稿日期: 2019-09-11
- 修回日期: 2019-12-01
- 刊出日期: 2020-02-10

Drug resistance analysis of influenza virus to neuraminidase inhibitor from 2018 to 2019 in Hebei Province

Institute of Prevention and Treatment for Viral Diseases, Hebei Center for Disease Control and Prevention, Shijiazhuang 050021, China

Funds: Hebei Medical Scientific Research Project of 2019(20190142)

More Information

Corresponding author: QI Shun-xiang, E-mail:hbcdc999@126.com

摘要

摘要: 目的分析河北省2018-2019年流感流行季节流感病毒对神经氨酸酶抑制剂类(neuraminidase inhibitor, NAI)药物的耐药情况, 为流感的预防控制提供依据。方法选取H1N1(pdm09)亚型毒株25株、H3N2亚型毒株11株共36株流感病毒毒株进行生物学耐药实验, 使用荧光发光法检测病毒对奥司他韦和扎纳米韦的药物敏感性。结果 2018-2019年河北省H1N1(pdm09)和H3N2亚型流感病毒全部对奥司他韦和扎那米韦敏感, 对奥司他韦的半数抑制浓度(half maximal inhibitory concentration, IC₅₀)平均数分别为0.50 nM(0.07~1.14 nM)和0.25 nM(0.09~0.69 nM), 对扎那米韦的IC₅₀平均数分别为0.29 nM(0.09~0.85 nM)和0.87 nM(0.17~1.81 nM), 均在相对应型别参考株IC₅₀值10倍以内。结论 2018-2019年河北省检测的流感毒株都对NAI类药物敏感。
- 流感病毒 /
- 神经氨酸酶抑制剂 /
- 耐药性
Abstract: Objective To analyze the resistance of influenza virus to neuraminidase inhibitors(NAI) in Hebei province during 2018-2019. Methods Virus were collected from the Hebei Influenza Surveillance Network during 2018-2019. A total of 36 confirmed influenza viruses(with 25 H1 pdm09 and 11 H3 N2) were selected to test resistance to oseltamivir and zanamivi with fluorescence(FL). Results All 36 influenza viruses tested were sensitive to oseltamivir and zanamivir. The median half maximal inhibitory concentration(IC₅₀) for oseltamivir of H1 pdm09 and H3 N2 were of 0.50 nM(range 0.07-1.14 nM) and 0.25 nM(range 0.09-0.69 nM) respectively, while 0.29 nM(range 0.09-0.85 nM) and 0.87(range 0.17-1.81 nM) for zanamivir, all were within 10 fold IC₅₀ of the reference virus(corresponding type). Conclusion All the tested influenza strains isolated in Hebei province during 2018-2019 were sensitive to NAI.
- Influenza virus /
- Neuraminidase inhibitor /
- Resistance

HTML全文

表 1 药物参考株对神经氨酸酶抑制剂药物的敏感性结果

Table 1. Sensitivity results of drug reference strains to neuraminidase inhibitor drugs

毒株名称	型别/亚型	NA基因氨基酸变异位点	耐药检测结果(nM)
毒株名称	型别/亚型	NA基因氨基酸变异位点	奥司他韦	扎纳米韦
A/California/12/2012	H1N1 pdm09	275H	0.71	0.20
A/Texas/23/2012	H1N1 pdm09	H275Y	274.90	0.30
A/北京海淀/1942/2014	H3N2	119E	0.12	0.88
A/Texas/12/2007	H3N2	E119V	65.38	0.90

下载: 导出CSV

表 2 2018-2019年河北省流感毒株对神经氨酸酶抑制剂药物的敏感性结果

Table 2. Sensitivity results of influenza strains to neuraminidase inhibitors in Hebei Province from 2018 to 2019

序号	毒株名称	型别/亚型	采集日期	分离地区	传代史	HA滴度	IC₅₀(nM)
序号	毒株名称	型别/亚型	采集日期	分离地区	传代史	HA滴度	奥司他韦	扎纳米韦
1	A/河北桥西/SWL1133/2019(H1)	H1N1 pdm09	2019-2-13	张家口	C1	32	1.14	0.28
2	A/河北路南/SWL18/2019(H1)	H1N1 pdm09	2019-01-01	唐山	C1	128	0.52	0.48
3	A/河北裕华/SWL112/2019(H1)	H1N1 pdm09	2019-01-01	石家庄	C1	32	0.45	0.20
4	A/河北桥东/SWL13/2019(H1)	H1N1 pdm09	2019-01-01	邢台	E2	32	0.57	0.85
5	A/河北运河/SWL13/2019(H1)	H1N1 pdm09	2019-01-01	沧州	C2	16	0.38	0.18
6	A/河北桃城/SWL13/2019(H1)	H1N1 pdm09	2019-01-01	衡水	E2	64	0.46	0.30
7	A/河北桥西/SWL1121/2019(H1)	H1N1 pdm09	2019/2/11	张家口	C1	16	0.40	0.21
8	A/河北桥东/SWL1143/2019(H1)	H1N1 pdm09	2019/2/12	邢台	C1	32	0.46	0.36
9	A/河北双桥/SWL1125/2019(H1)	H1N1 pdm09	2019/2/8	承德	C2	128	0.59	0.32
10	A/河北运河/SWL1190/2019(H1)	H1N1 pdm09	2019/2/6	沧州	E1	32	0.62	0.30
11	A/河北海港/SWL1567/2018(H1)	H1N1 pdm09	2018/10/28	秦皇岛	C1	32	0.63	0.66
12	A/河北海港/SWL1515/2018(H1)	H1N1 pdm09	2018/10/23	秦皇岛	C2	64	0.45	0.34
13	A/河北海港/SWL1510/2018(H1)	H1N1 pdm09	2018/10/20	秦皇岛	C2	64	0.55	0.36
14	A/河北海港/SWL1648/2018(H1)	H1N1 pdm09	2018/11/30	秦皇岛	C1	16	0.57	0.33
15	A/河北海港/SWL1647/2018(H1)	H1N1 pdm09	2018/11/30	秦皇岛	C1	16	0.77	0.22
16	A/河北海港/SWL1642/2018(H1)	H1N1 pdm09	2018/11/29	秦皇岛	C1	16	0.38	0.16
17	A/河北海港/SWL1637/2018(H1)	H1N1 pdm09	2018/11/24	秦皇岛	C1	32	0.07	0.10
18	A/河北海港/SWL1634/2018(H1)	H1N1 pdm09	2018/11/21	秦皇岛	C1	16	0.68	0.14
19	A/河北邯山/SWL148/2019(H1)	H1N1 pdm09	2019/1/8	邯郸	C1	64	0.33	0.23
20	A/河北承德/SWL1612/2018(H1)	H1N1 pdm09	2018/12/26	承德	C1	64	0.26	0.09
21	A/河北长安/SWL1676/2018(H1)	H1N1 pdm09	2018/12/19	石家庄	C1	256	0.54	0.29
22	A/河北裕华/SWL1593/2018(H1)	H1N1 pdm09	2018/12/19	石家庄	C1	64	0.49	0.18
23	A/河北桃城/SWL1800/2018(H1)	H1N1 pdm09	2018/12/14	衡水	C1	16	0.46	0.18
24	A/河北海港/SWL1662/2018(H1)	H1N1 pdm09	2018/12/4	秦皇岛	C1	32	0.24	0.24
25	A/河北路南/SWL11319/2018(H1)	H1N1 pdm09	2018/12/28	唐山	C1	64	0.58	0.18
26	A/河北鹿泉/1102/2019(H3)	H3N2	2019/1/29	石家庄	C1	32	0.10	0.17
27	A/河北新华/137/2019(H3)	H3N2	2019-01-08	石家庄	C2	16	0.57	0.46
28	A/河北鹿泉/18/2019(H3)	H3N2	2019-01-07	石家庄	C2	16	0.69	0.32
29	A/河北鹿泉/1108/2019(H3)	H3N2	2019/2/11	石家庄	C2	16	0.35	0.30
30	A/河北邯山/1241/2019(H3)	H3N2	2019/2/6	邯郸	C1	32	0.09	1.37
31	A/河北邯山/1238/2019(H3)	H3N2	2019/2/7	邯郸	C1	64	0.11	1.78
32	A/河北邯山/1235/2019(H3)	H3N2	2019/2/5	邯郸	C1	64	0.22	1.31
33	A/河北邯山/1229/2019(H3)	H3N2	2019/2/5	邯郸	C1	32	0.17	1.58
34	A/河北邯山/1223/2019(H3)	H3N2	2019/2/5	邯郸	C1	32	0.12	1.81
35	A/河北莲池/11350/2018(H3)	H3N2	2018/12/25	保定	C2	16	0.11	0.18
36	A/河北莲池/11292/2018(H3)	H3N2	2018/12/17	保定	C2	32	0.26	0.27

下载: 导出CSV

参考文献(15)

[1]	李兰娟, 任红.传染病学[M].第8版.北京: 人民卫生出版社, 2013: 55. Li LJ, Ren H. Infectious Diseases[M]. 8th ed. Beijing: People's Medical Publishing House, 2013: 55.
[2]	邢晓会, 赵翔, 李希妍, 等.全球B型流感病毒耐药相关突变株NA和HA序列特征分析[J].中国人畜共患病学报, 2013, 29(10): 946-950. DOI: 10.3969/cjz.j.issn.1002-2694.2013.10.002. Xing XH, Zhao X, Li XY, et al. Characterization of the hemagglutinin and neuraminidase of global influenza B virus with drug-resistance[J]. Chin J of Zoo, 2013, 29(10): 946-950. DOI: 10.3969/cjz.j.issn.1002-2694.2013.10.002.
[3]	赵升, 僧明华, 吕宛玉, 等. 2017-2018年河南省流感病毒对神经氨酸酶抑制剂药物的耐药性研究[J].中华疾病控制杂志, 2019, 23(3): 259-262. DOI: 10.16462/j.cnki.zhjbkz.2019.03.003. Zhao S, Seng MH, Lu WY, et al. Resistance of influenza virus in Henan Province to neuraminidase inhibitor from 2017 to 2018[J]. Chin J Dis Control Prev, 2019, 23(3): 259-262, 288. DOI: 10.16462/j.cnki.zhjbkz.2019.03.003.
[4]	Nguyen HT, Sheu TG, Mishin VP, et al. Assessment of pandemic and seasonal influenza A(H1N1)virus susceptibility to neuraminidase inhibitors in three enzyme activity inhibition assays[J]. Antimicrob Agents Chemother, 2010, 54(9): 3671-3677. DOI: 10.1128/AAC.00581-10.
[5]	Okomo-Adhiambo M, Sleeman K, Ballenger K, et al. Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective[J]. Viruses, 2010, 2(10): 2269-2289. DOI: 10.3390/v2102269.
[6]	中国国家流感中心.全国流感监测技术指南(2017年版). [EB/OL]. (2017-09-30)[2019-12-01]. http://www.chinaivdc.cn/cnic/zyzx/jcfa/201709/t20170930_153976.htm. Chinese National Influenza Center.National technical guidelines for influenza surveillance (2017edition).[EB/OL].(2017-09-30)[2019-12-01].http://www.chinaivdc.cn/cnic/zyzx/jcfa/201709/t20170930_153976.htm.
[7]	Nitsch-Osuch A, Brydak LB. Influenza viruses resistant to neuraminidase inhibitors[J]. Acta Biochim Pol, 2014, 61(3): 505-508.
[8]	Matrosovich MN, Matrosovich TY, Gray T, et al. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium[J]. J Virol, 2004, 78(22): 12665-12667. DOI: 10.1128/JVI.78.22.12665-12667.2004.
[9]	Yang X, Steukers L, Forier K, et al. A beneficiary role for neuraminidase in influenza virus penetration through the respiratory mucus[J]. PLoS One, 2014, 9(10): e110026. DOI: 10.1371/journal.pone.0110026.
[10]	Du R, Cui Q, Rong L. Competitive cooperation of hemagglutinin and neuraminidase during influenza A virus entry[J]. Viruses, 2019, 11(5). DOI: 10.3390/v11050458.
[11]	Hurt AC, Besselaar TG, Daniels RS, et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015[J]. Antiviral Res, 2016, 132: 178-185. DOI: 10.1016/j.antiviral.2016.06.001.
[12]	陈寅, 茅海燕, 周敏, 等.浙江省近年来甲型H1N1流感病毒神经氨酸酶基因序列分析[J].疾病预测, 2013, 28(10): 811-814. DOI: 10.3784/j.issn.1003-9961.2013.10.007. Chen Y, Mao HY, Zhou M, et al. Sequence analysis of neuraminidase gene of influenza A(H1N1)pdm09 viruses in Zhejiang Province[J]. Disease Surveillance, 2013, 28(10): 811-814. DOI: 10.3784/j.issn.1003-9961.2013.10.007.
[13]	李娟, 赵晓南, 曹艺会, 等.云南省2009-2014年甲型H1N1流感病毒HA及NA基因特征分析[J].病毒学报, 2015, 31(6): 674-678. DOI: 10.13242/j.cnki.bingduxuebao.002829. Li J, Zhao XN, Cao YH, et al. Characterization of the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 virus from 2009 to 2014 in Yunnan[J]. Chin J of Viro, 2015, 31(6): 674-678. DOI: 10.13242/j.cnki.bingduxuebao.002829.
[14]	谢剑峰, 张炎华, 赵琳, 等.一株达菲耐药的甲型H1N1流感病毒全基因特征分析[J].中国微生态学杂志, 2016, 28(8): 884-888. DOI: 10.13381/j.cnki.cjm.201608004. Xie JF, Zhang YH, Zhao L, et al. Characteristics of complete genome of an Oseltamivir-resistant influenza A(H1N1)pdm09 virus[J]. Chin J Microecol, 2016, 28(8): 884-888. DOI: 10.13381/j.cnki.cjm.201608004.
[15]	刘瑞弘, 文奇, 付倩, 等.新余市甲型H1N1流感病毒H275Y突变监测[J].实验与检验医学, 2018, 36(4): 472-474. DOI: 10.3969/j.issn.1674-1129.2018.04.003. Liu RH, Wen Q, Fu Q, et al. Surveillance of influenza A(H1N1)pdm09 virus with H275Y mutation in Xinyu[J]. Experimental and Laboratory Medicine, 2018, 36(4): 472-474. DOI: 10.3969/j.issn.1674-1129.2018.04.003.