新余市甲型流感病毒M基因进化及金刚烷胺类耐药性分析

目的分析新余市2013年-2015年甲型流感病毒M基因进化及金刚烷胺类耐药情况,为临床治疗和疾病防控提供依据。方法随机选择30株甲型流感病毒,经核酸提取、one-step RT-PCR扩增M基因片段和双向序列测定,通过DNAStar5.0和Mage5.0序列分析软件获得有关数据。结果在M基因上,16株H3N2毒株、14株新型H1N1毒株核苷酸序列的同源性分别99.2%、98.8%,且与相应的疫苗推荐株高度同源,H3N2毒株与新型H1N1毒株与相应的疫苗推荐株相比较,大部分(13/16)H3N2毒株未发生变异,所有新H1N1毒株均发生1~2个氨基酸替换;30株新余市甲型流感毒株M2蛋白第31位氨基酸位点均由丝氨酸(S)突变为天冬酰胺(N)。结论新余市2013年至2015年甲型流感毒株相同亚型间M基因同源性较高,30株甲型流感毒株均具有金刚烷胺类药物抗性,对流感病毒耐药性问题应该给予重视。     

2016-2017年我国甲型流感病毒H3N2亚型HA和NA基因的分子特征分析

目的探讨2016-2017年我国甲型流感病毒H3N2亚型血凝素(hemagglutinin,HA)和神经氨酸酶(neuraminidase,NA)基因的分子特征,为甲型流感病毒H3N2亚型的防控提供科学依据。方法从全球共享禽流感数据库(GISAID)中获得我国2016~2017年分离的525株甲型流感病毒H3N2亚型病毒和13株H3N2亚型参考株的HA和NA基因序列。应用MEGA 6.0软件分析HA和NA的分子进化特征、氨基酸位点和耐药位点的变异情况。结果进化树分析显示13株参考株之间HA和NA氨基酸的同源性均为96.9%~99.1%。2016-2017年我国甲型流感病毒H3N2亚型的病毒株HA和NA氨基酸序列之间同源性均为96.3%~100%,HA和NA的优势亚分支均为3C.2a.1,相当一部分毒株分型不够明确。HA氨基酸变异分析显示9株发生N121E突变,103株发生N121K的突变且主要来源于2017年的香港毒株;182株发生G/R142K突变;A/Hong_Kong/3079/2017-HA和A/Guangdong-Chengguan/1383/2017-HA均发生A128I突变;NA蛋白仅3株(A/Hunan-Suxian/1980/2016-NA、A/Hunan-Yuhua/11799/2016-NA和A/Ningxia-Yuanzhou/1657/2016-NA)发现H275Y耐药位点突变。结论 2016-2017年我国甲型流感病毒H3N2亚型的HA和NA蛋白与参考株间存在一定的差异,优势亚型均为3C.2a.1;与病毒的毒力及药物相关的部分关键氨基酸位点发生变异。应密切关注H3N2病毒的分子特征,为其防控提供参考。     

2017-2020年湖北省甲型H3N2亚型流感病毒流行特征和进化分析

目的 了解2017-2020年湖北省甲型H3N2亚型流行性感冒(流感)流行分布及基因进化情况.方法 根据湖北省流感病原学监测数据,分析2017-2020年甲型H3N2亚型流感病毒流行分布情况,按年度分布和地域分布的原则选取2017-2020年各市级流感监测网络实验室送检的该亚型流感病毒共38株进行测序,获得病毒HA和N...     

2007-2009年广西壮族自治区流行性感冒监测结果分析

目的监测广西流行性感冒(流感)流行状况和流感病毒优势株的变化,探索广西流感流行规律。方法在国家级哨点医院,对流感样病例进行逐日统计,对符合条件的流感样病例进行采样,采用细胞培养法分离鉴定流感病毒。结果2007-2009年广西流感监测医院的流感样病例以春、夏季高峰明显。2007-2009年广西流感监测医院的流感样病例数占门诊总病例数的年平均数分别为11.34%、12.45%和7.10%。2007年分离134株流感病毒,其中B型58株,A型H3N2亚型69株,H1N1亚型7株。2008年分离82株流感病毒,其中B型33株,A型H3N2亚型30株,H1N1亚型19株。2009年分离1737株流感病毒,其中B型192株,A型H3N2亚型176株,H1N1亚型74株,甲型H1N1295株。结论2007-2009年广西流感监测医院的流感样病例全年均有发生,以春、夏季为高发季节。2007、2008年的主要流行株都为H3N2亚型和B型流感毒株,2009年的主要流行株为甲型H1N1流感毒株。     

2008-2010年广西边境地区流感和人禽流感监测结果分析

目的 对广西壮族自治区(广西)8个边境市(县)所属的综合性医院不明原因肺炎、病原待查重症肺炎和流感样病例开展病原学监测,了解广西边境地区流感病毒优势株及其变化,探索广西边境地区流感流行规律,为科学防控边境地区流感和人禽流感提供依据。 方法 在边境地区医院设置监测点,开展相关病例监测,提取监测病例咽拭子标本病毒核酸,反转录合成cDNA,多重 PCR扩增目的基因,电泳检测扩增产物;采用细胞培养法分离鉴定流感病毒;采集从事饲养、销售和屠宰家禽的职业人群的静脉血34份,通过血凝抑制实验进行禽流感H5亚型抗体检测。 结果 2008年广西边境地区分离到6株流感病毒,其中B型5株,H1N1亚型1株;2009年分离到33株流感病毒,其中B型17株,H3N2亚型8株,H1N1亚型2株,甲型H1N1 6株;2010年分离到流感毒株130株,其中B型55株,H3N2亚型49株,H1N1亚型1株,甲型H1N1 25株;2008-2010年检测不明原因肺炎、病原待查的重症肺炎标本9份,人禽流感核酸和多重呼吸道病毒核酸检测均为阴性;采集从事饲养、销售和屠宰家禽的职业人群血样本34份,未检出 H5N1亚型禽流感病毒抗体阳性的标本。 结论 2008年和2009年广西边境地区的流感优势株为B型流感毒株,2010年为B型和H3N2亚型流感毒株;从有限的不明原因肺炎和病原待排查的重症肺炎病例标本中未检出禽流感病毒;禽流感H5亚型在职业暴露人群中未发现隐性感染。进一步加强对广西边境地区的流感和人禽流感病原学监测工作,对广西的流感和人禽流感的防控工作有重要意义。     

2013年-2015年景德镇市流感病原学监测分析

目的：分析景德镇市近3年流感病原学监测数据,为流感防控提供参考。方法采集哨点医院流感样病例和不明原因肺炎的咽拭子标本,通过Real-PCR方法对标本进行流感病毒核酸检测和分型,流感病毒核酸检测阳性标本接种到MDCK细胞进行病毒分离,以人红细胞凝集及凝集抑制试验对流感病毒进行鉴定分型。结果共采集标本2554份,核酸检测阳性标本265份,分离出流感病毒184株,新甲型H1N1、A（H3N2）亚型和B型毒株均有发现。2013.4-2014.3年以新甲型H1N1和A(H3N2)为流行优势株,B型毒株两个系都有出现,但新甲型H1N1从2014年3月之后就没有再次出现;2014.4-2015.9主要流行株则为A（H3N2及B（Yamagata）少量出现的特点。数核酸阳性A(H3N2)亚型流感的MDCK细胞阳性分离率从85.71%降至59.02%,病毒血凝抑制效价也从1280降低到最低的40;核酸阳性B型流感病毒的MDCK细胞阳性分离率从62.07%上升到90.91%,病毒血凝抑制效价一般都在1280及以上。结论景德镇地区2013年4月-2015年9月期间,流感流行表现为新甲型（H1N1）短暂流行后,夏季主要以A(H3N2)流感为主,冬春季以B（Yamagata）型流感高发;A(H3N2)亚型的分离率逐年降低,B型流感病毒分离率上升;A（H3N2）亚型的抗原性变异较大,而B型的抗原性较稳定。     

长春市2018-2020监测年度甲型H1N1流感病毒神经氨酸酶（NA）基因特征分析

目的 分析长春市2018-2020年度甲型H1N1流感病毒神经氨酸酶（NA）基因特征,了解其变异情况及遗传进化特征。方法 选取2018-2020年度甲型H1N1流感病毒分离株72株,PCR扩增NA基因并进行序列测定;利用生物信息学软件对分离株的NA基因进行进化和变异分析。结果 长春市72株分离株与疫苗株A/California/07/2009的NA蛋白相比均有V13I、I34V、L40I、N44S、V81A、N200S、V241I、N248D、N270K、Y351F、N369K、N386K、K432E、N449D共同的氨基酸位点变异,且有1株发生了NA蛋白H275Y耐药位点的突变,提示此毒株为奥司他韦耐药株。72株病毒株NA基因之间核苷酸同源性为97.6%-100%,氨基酸同源性为97.2%-100%。在进化树分析上,呈集中分布态势,都属于6B.1分支。结论 长春市2018-2020年度甲型H1N1流感病毒神经氨酸酶基因持续发生变异,但大部分甲型H1N1流感病毒仍对神经氨酸酶抑制剂敏感。未来仍应加强耐药性监测,为预防甲型H1N1流感大流行提供参考。     

2017-2020年流感流行季节河北省甲型H1N1流感病毒耐药性及耐药基因分析

  目的  分析河北省2017 — 2020年流感流行季节甲型H1N1流感病毒对神经氨酸酶抑制剂类药物（NAI）的耐药情况,为流感的预防控制提供依据。  方法  选取2017 — 2020年流感流行季节37株甲型H1N1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那米韦的药物敏感性。 选取38株甲型H1N1流感病毒提取核酸后对神经氨酸酶NA基因进行PCR扩增,测序后对耐药位点进行分析。  结果  选取的“A/河北新华/SWL1106/2017”对奥司他韦敏感性降低（IC₅₀=30.98 nmol/L）,其余36株甲型H1N1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（IC₅₀）平均数为0.46 （0.07～1.14 ）nmol/L;对扎那米韦的IC₅₀平均数为0.27 （0.07～0.85 ）nmol/L。 序列分析发现1株发生了H275Y突变,为奥司他韦耐药株。  结论  2017—2020年河北省流行的绝大部分甲型H1N1流感病毒对NAI类药物敏感。     

新余市甲型H1N1流感病毒H275Y突变监测

目的分析2013年-2014年新余市甲型H1N1流感病毒神经氨酸酶(NA)第275位氨基酸变异情况,掌握甲型H1N1流感病毒耐药特性。方法收集新余市流感监测哨点医院的流感样病例的咽拭子标本,采用狗肾传代细胞(MDCK)对标本进行病毒分离,随机选择15株甲型H1N1流感病毒进行核酸提取,采用逆转录-聚合酶链反应(RT-PCR)扩增病毒NA基因部分片段,应用限制性内切酶片段长度多态性分析(RFLP)方法进行酶切分析。结果新余市15株甲型H1N1流感病毒中,仅有A/江西渝水/SWL1220/2014(H1)发生了H275Y突变,它具有Oseltamivir耐药性。结论新余市绝大多数甲型H1N1流感毒株对Oseltamivir敏感,但仍有必要持续监测和防范Oseltamivir耐药毒株的出现。     

2009－2018年湖南省甲型H1N1亚型流感病毒监测结果及其全基因组进化分析

目的分析2009 — 2018年湖南省流感哨点医院甲型H1N1亚型流感监测结果,对分离病毒全基因组进化情况和分子特征进行分析。方法在全省14个市州的23家哨点医院开展流感监测工作,每周每家哨点医院门诊采集5 ~ 20份流感样病例的咽拭子标本进行核酸检测和/或病毒分离。 对分离的毒株全基因测序,使用BEAST软件贝叶斯方法构建基因进化树,序列与疫苗株进行比较。结果2009 — 2018年湖南省流感监测哨点医院共采集流感样病例标本190 289份,其中甲型H1N1流感阳性8 014份,阳性率为4.21%。 时间分布共有7个较明显的流行高峰,峰值以2009年最高。 1 ~ 5岁（占25.13%）和5 ~ 15岁（占32.83%）年龄组所占比重较多,人群男女性别比为1.23∶1。 对分离的60株甲型H1N1亚型流感病毒进行同源性分析,与疫苗株相比全基因组序列的同源性在97.2% ~ 99.9%之间。 贝叶斯基因进化树呈现阶梯状生长。 推断最早的公共祖先出现在2 009.177年,平均进化速率为2.695×10?3个替换?位点?1?年?1。 贝叶斯天际线模型分析甲型H1N1流感的种群动态2009 — 2018年间基本维持稳定。 表面蛋白选择压力分析dN/dS值为0.201与0.219。 表面蛋白血凝素分子的主要变异位点为L8M、S91R、S160G、S181T、A214T、I312V。 2株病毒神经氨酸酶分子出现H275Y耐药位点的突变。结论2009 — 2018年湖南省每年甲型H1N1流感阳性率和甲型H1N1流感所占流感比例各不相同,流行高峰出现在冬季,病例以儿童和少年为主,病毒基因持续变异,种群动态稳定。     

2016-2020年吉林省流感病原学监测分析

目的 了解2016-2020年吉林省流感病毒的流行趋势、病原学变化特点,为本省流感防控提供科学依据.方法 对吉林省13家流感监测哨点医院报告的流感样病例(ILI)进行统计学分析,对采集的流感样病例标本进行实验室检测和病原学监测分析.结果 2016-2020年度ILI就诊比例呈逐年上升的趋势,4个监测年度报告的ILI比例...     

Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds

Subtype-specific neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) have been reported during in vitro passages and in clinic. In this study, we evaluated the impact of various NA mutations (E119A/G/V, H274Y, R292K and N294S) on the susceptibility profiles to different NAIs (oseltamivir, zanamivir and peramivir) using recombinant NA proteins of influenza A/WSN/33 (H1N1) and A/Sydney/5/97-like (H3N2) viruses. In the Nl subtype, the E119V mutation conferred cross-resistance to oseltamivir, zanamivir and peramivir [1,727-2,144 and 5,050-fold increase in IC50 values compared with wild-type (WT)] whereas only oseltamivir-resistance (1,028-fold increase in IC50) was conferred by the same mutation in the N2 subtype. The N294S mutation conferred resistance to oseltamivir in both the NI and N2 subtypes (197- and 1,879-fold increase in IC50 values, respectively) whereas the H274Y mutation conferred resistance to oseltamivir (754-fold increase) and peramivir (260-fold increase) in the N1 subtype only. The virulence of reverse genetics-rescued A/WSN/33 viruses harbouring H274Y and N294S NA mutations was investigated in Balb/c mice. The WT and H274Y recombinants had identical LD50 values (103 PFUs) and generated similar viral lung titres, whereas a higher LD50 (10 PFUs) and a 1-log decrease in viral lung titres were obtained with the N294S mutant. This study shows that some NA mutations at framework residues may confer resistance to one or three NAIs depending on the viral subtype. It suggests that certain drug-resistant NA mutants may still be virulent although additional studies using clinical isolates are needed to confirm our results.     

Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates

The number of patients infected with H7N9 influenza virus has been increasing since 2013. We examined the efficacy of neuraminidase (NA) inhibitors and the efficacy of a vaccine against an H7N9 influenza virus, A/Anhui/1/2013 (H7N9), isolated from a patient in a cynomolgus macaque model. NA inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with R289K or I219T in NA [residues 289 and 219 in N9 of A/Anhui/1/2013 (H7N9) correspond to 292 and 222 in N2, respectively] in three of the six treated macaques, whereas subcutaneous immunization of an inactivated vaccine derived from A/duck/Mongolia/119/2008 (H7N9) prevented propagation of A/Anhui/1/2013 (H7N9) in all vaccinated macaques. The percentage of macaques in which variant H7N9 viruses with low sensitivity to the NA inhibitors were detected was much higher than that of macaques in which variant H5N1 highly pathogenic influenza virus was detected after treatment with one of the NA inhibitors in our previous study. The virus with R289K in NA was reported in samples from human patients, whereas that with I219T in NA was identified for the first time in this study using macaques, though no variant H7N9 virus was reported in previous studies using mice. Therefore, the macaque model enables prediction of the frequency of emerging H7N9 virus resistant to NA inhibitors in vivo. Since H7N9 strains resistant to NA inhibitors might easily emerge compared to other influenza viruses, monitoring of the emergence of variants is required during treatment of H7N9 influenza virus infection with NA inhibitors.     

Characterization of Drug-Resistant Influenza Virus A(H1N1) and A(H3N2) Variants Selected In Vitro with Laninamivir

Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses under in vitro laninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant. In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistance in vitro.     

Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC(50)s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC(50)s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC(50)s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC(50)s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC(50)s were above the 95% confidence limits and several control isolates for which the IC(50)s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.     

2010年广州市甲型H1N1流感病毒分离株NA基因变异分析

目的比较2010年从广州市分离到的甲型H1N1流感病毒神经氨酸酶(NA)基因与2009年中国大陆甲型H1N1流感病毒NA基因的变异情况,为甲型H1N1流感的监测和防控提供参考资料。方法收集2010年广州市有发热和呼吸道症状患者的咽拭子标本,用甲型H1N1流感病毒特异性引物进行聚合酶链反应(PCR)检测,扩增分离到的甲型H1N1流感病毒NA基因片段,测序后与2009年的H1N1毒株进行比对和进化分析,并用生物信息学方法对耐药位点和糖基化位点进行分析。结果共收集1 194份咽拭子标本,检测到甲型流感病毒阳性327份,其中H1N1流感病毒6株,与2009年分离的甲型H1N1流感病毒相比,有16个位点发生了有义突变,3个位点和NA活性相关,其中222位氨基酸的变异位于NA活性位点上。结论成功扩增了2010年广州市6株甲型H1N1流感病毒株NA基因并测序,未发现H275Y耐药位点的变异。3毒株在NA活性位点222位、228位和425位等氨基酸位点处发生了变异,需继续加强监测。     

Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008

The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC₅₀s) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC₅₀s, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC₅₀ value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.     

赣州市2014年新型甲型H1N1流感病毒NA基因特征及耐药性分析

目的：分析江西省赣州市2014年新型甲型H1N1流感病毒NA基因的特点,掌握其耐药情况,为临床治疗和疾病控制提供参考依据。方法随机选择17株新型甲型H1N1流感病毒,经核酸提取和one-step RT-PCR扩增NA基因片段,双向序列测定,采用DNAStar5.0和Mage4.0序列分析软件分析NA基因特征以及耐药性位点。结果17株毒株的NA基因片段与代表株A/California/07/2009(H1N1)的序列核苷酸序列进行比对,核苷酸序列同源性高达98.4%以上,氨基酸的同源性也高达97.0%以上。17株毒株的NA活性中心位点氨基酸及周围的辅助位点氨基酸均未发生氨基酸替换。结论17株毒株的NA基因片段保持高度的同源性并均对流感病毒神经氨酸酶抑制剂药物敏感,但仍应加强对流感病毒的耐药性监测,为制定新型甲型H1N1流感的防制措施提供技术支持。     

2017-2019年度上海市松江区A(H1N1)pdm09流感病毒HA和NA基因特征分析

目的 分析上海市松江区2017-2019监测年度A(H1N1)pdm09流感病毒HA和NA基因特征.方法 对松江区分离的毒株随机挑选46株A(H1N1)pdm09流感病毒毒株进行HA和NA基因序列进化分析和氨基酸位点变异分析,采用神经氨酸酶抑制实验开展奥司他韦和扎那米韦敏感性监测.结果 A(H1N1)pdm09流感病毒...