A Historical Perspective of Influenza A(H1N2) Virus

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.     

珠海市2006-2008年流感症状监测分析及预测

目的 了解广东省珠海市2006-2008年流感流行趋势及其病毒株变化特点,预测2009年流行趋势,为本地区防控流感提供科学依据.方法 收集2006-2008年珠海市流感监测哨点流感样病例(ILl)监测和暴发疫情监测资料信息,医院门诊、暴发疫情的流感病毒病原学监测资料,进行综合分析.采用季节性自回归移动平均(ARIMA)构建模型预测2009年ILI的趋势.结果 2006-2008年珠海市流感流行大致呈3-4月和6-7月的双峰型,平均ILI%为4.1%;门诊报告ILI中<5岁儿童为主,占50.3%,构成比逐年上升.哨点医院流感病毒分离阳性率为10.0%,2006年流感季节类型为A(H1N1)型和B型混合型,2007年为A(H3N2)型占优势,2008年为A(H1N1)型和A(H3N2)型混合型.暴发疫情主要发生在3-6月,流行病毒株与医院哨点监测基本一致.结论 珠海市流感流行呈现春夏季双峰型,ILI的高峰较流感病毒早4周左右;H3型、H1型、B型流感病毒交替成为年分离优势株.预测2009年季节性流感流行趋势平稳.     

Influenza A Viruses of Human Origin in Swine,Brazil

The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.     

1991～2000年广东省流感监测结果分析

目的 了解流感流行和流感病毒毒株表面抗原性变异情况。方法 用9～11d龄鸡胚和(或)麦克丁氏犬肾(MDCK)细胞分离流感病毒，病毒鉴定用常量红细胞凝集抑制法(HI)；鸡血清流感抗体检测采用微量半加敏红细胞凝集抑制法(HI)。结果 1991～2000年全省未发生流感大流行。期间从人群中共分离流感病毒1008株，以A(H3N2)亚型流感病毒(62．3％)、B型流感病毒(26．6％)为主。从人群中分离出10株H9N2亚型禽流感病毒。从鸡群中分离到H9N2亚型禽流感病毒98株。A(H3N2)亚型病毒的抗原性不断发生漂移。结论 除1993、1995年未分离到A(H1N1)亚型流感病毒外。其它8年均分离到A(H1N1)、A(H3N2)、B型流感病毒。1998、1999年还同时分离到H9N2亚型禽流感病毒。并证实了A(H3N2)亚型病毒表面抗原的易变性；鸡群中有多个A亚型流感病毒同时存在，必须做好流感监测。     

Antibodies cross-reactive to influenza A (H3N2) variant virus and impact of 2010-11 seasonal influenza vaccine on cross-reactive antibodies - United States

Since August 2011, a total of 12 human infections with influenza A (H3N2) variant viruses with genes from avian, swine, and human viruses (i.e., A [H3N2]v) that had acquired the M gene from influenza A (H1N1)pdm09 virus have been reported to CDC. Eleven of the cases occurred in children aged <10 years. In six cases, no history of recent exposure to swine was noted, suggesting that human-to-human transmission had occurred. This new gene constellation for A (H3N2)v viruses and its temporal association with an increase in human cases of A (H3N2)v highlight the need to better understand the risk for human infection with these viruses and the extent to which current seasonal vaccines might elicit cross-reactive antibodies to them. CDC conducted a preliminary analysis to evaluate the age-specific presence of serum cross-reactive antibody in U.S. populations vaccinated or not vaccinated with the 2010-11 seasonal trivalent influenza vaccine (TIV). The results indicated that 1) little or no cross-reactive antibody to A (H3N2)v exists among children aged <10 years, 2) immunization with the 2010-11 TIV had no impact on cross-reactive antibody levels in those aged <3 years, 3) cross-reactive antibody was detected in 20%-30% of those aged ≥10 years, and 4) among adults, vaccination with TIV provided a modest boost to the level of cross-reactive A (H3N2)v antibodies. Receipt of seasonal influenza vaccine continues to be recommended to protect against circulating human influenza viruses for all age groups and might provide limited protection against A (H3N2)v infection in the adult population. A vaccine virus specific for A (H3N2)v has been developed and could be used to produce an H3N2v vaccine, if needed.     

Influenza virus-like particles comprised of the HA, NA, and M1 proteins of H9N2 influenza virus induce protective immune responses in BALB/c mice

Avian influenza viruses represent a growing threat for an influenza pandemic. To develop recombinant vaccine for avian influenza of the H9N2 subtype, we expressed in insect cells virus-like particles (VLPs) consisting of three structural proteins of influenza A/Hong Kong/1073/99 (H9N2) virus. Upon infection of Sf9 cells with recombinant baculoviruses, the hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins were co-expressed in the infected cells, self-assembled, and released into the culture medium as VLPs of 80–120 nm in diameter. VLPs exhibited functional characteristics of influenza virus including hemagglutination and neuraminidase activities. In BALB/c mice, VLPs elicited serum antibodies specific for influenza A/Hong Kong/1073/99 (H9N2) virus and inhibited replication of the influenza virus after challenge. Thus, VLPs represent a potential strategy for the development of human vaccines against avian influenza H9N2 viruses.     

Swine-origin influenza A (H3N2) virus infection in two children--Indiana and Pennsylvania, July-August 2011

Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine. Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission.     

上海市人群甲型流感病毒H1、H3、H5、H9抗体血清学监测

[目的 ]　了解上海市人群对甲 3型、甲 1型流感病毒和禽流感病毒H9、H5的抗体 ,探讨甲 3型、甲 1型流感流行的趋势和禽流感病毒H9、H5抗体存在情况。　 [方法 ]　应用常规血凝抑制试验微量半加敏法对上海市不同年龄组人群进行甲型流感抗体血清学监测。　 [结果 ]　对A/SH/1/98(H3N2 )毒株的抗体阳性率为 96.2 0 % ;对A/SH /7/99(H1N1)毒株的抗体阳性率为 72 .60 % ;对H9毒株的抗体阳性率为 7.5 6% ;对H5毒株的抗体阳性率仅 0 .75 %。　 [结论 ]　A/SH/1/98(H3N2 )类毒株已不可能在上海再度引起流行 ;A/SH/7/99(H1N1)类毒株今后在人群中 ,特别在 0～ 4岁年龄组中可能存在散在性发生或局限性小爆发 ;本市人群曾受到禽流感H 9病毒的感染 ,不能排除由本市禽类中的H9病毒感染及人的可能 ;受禽流感H5毒株感染只是个别现象。禽流感病毒在本市禽类中的感染状况及对人的影响需进一步研究     

Serological studies of influenza viruses in pigs in Great Britain 1991-2.

Samples from a sow serum bank representative of the pig population of Great Britain collected during 1991-2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of classical swine H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9.9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.     

湖南省2006--2009年人感染高致病性禽流感病毒(H5N1)分子特征研究

目的 分析湖南省2006-2009年4例人感染高致病性禽流感病例感染病毒的可能来源、基因重配情况以及分子特征.方法 鸡胚分离核酸检测H5N1病毒阳性标本,获得高致病性H5N1病毒,对病毒进行全基因组序列测定,采用BLAST和MEGA4.0进行同源性比对、基因进化分析和各基因分子特征分析.结果 4株病毒的基因片段均为禽源,并未发现与人季节性流感病毒之间发生重配,且与当地禽类中分离的病毒高度同源.全基因组进化树分析显示,4株病毒在分支2.3.4中,2株为基因型V、2株为新的基因型.分子特征分析显示,4株病毒的血凝素(HA)分子裂解位点均为PLRERRKR/G,均出现A160T位点突变,神经氨酸酶(NA)分子49～68位均出现20个氨基酸(aa)缺失,非结构蛋白1(NSI)分子80～84位均出现5个aa的缺失.在HA分子大部分位点,4株病毒仍然表现出与禽类受体的亲和性,HN/1/09和HN/2/09出现可能使病毒对α-2,6连接的唾液酸人类受体的亲和性增强的T192I突变.HN/1/08的PB2基因出现增加小鼠致病力的D701N改变.耐药性基因片段分析显示,4株病毒对金刚烷胺和奥司他韦均敏感.结论 2006-2009年湖南省4株人感染高致病性禽流感病毒(H5N1)为禽源,但存在多种基因型,而且发生了部分位点的突变.

Abstract：

Objective To understand the possible origins,genetic re-assortment and molecular characterization of 4 highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province,between 2006 and 2009,Methods H5N1 PCR test-positive specimens were inoculated in embryonated eggs while H5N1 virus was isolated and genomes sequenced.Genome homology and genetic molecular characterization were analyzed by BLAST and MEGA 4.0.Results All gene segments of the 4 viruses were avian in origin.No re-assortment was found between avian influenza A(H5N1)viruses and human seasonal influenza viruses.Virnses that isolated from domestic poultry shared high similarity with the 4 human viruses in gene homology.Data from the whole genome phylogenetic analysis showed that the 4 viruses were in clade 2.3.4,while 2 viruses belonged to genotype V,and another 2 were new genotypes.Results from molecular characterization showed that amino acid sequences of HA cleavage site of the 4 viruses were PLRERRKR/G.All 4 viruses had A160T mutation in HA,a 20 amino acid deletion in the neuraminidase(NA)stalk at position 49-68,and a 5 amino acid deletion in the non-structural protein 1(NS1).Most sites in the HA molecules showed that the viruses preferentially bound to avian influenza virus receptor.However,T192I mutation that might enhance the α2,6-linked sialic acid human influenza receptor binding had emerged in HN/1/09 and HN/2/09.D701N mutation of PB2 that increased the virulence in mice was found in HN/1/08.Analysis on drug resistance gene amino acid showed that all 4 viruses were sensitive to amantadine and oseltamivir.Conclusion Highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province from 2006 to 2009 were avian in origin,and the 4 viruses belonged to different genotypes.Some mutations that related to virulence and receptor binding positions had emerged in some of the strains.     

Influenza activity in China: 1998-1999

During 1989-1999, influenza A H3N2 and H1N1 subtypes and B type viruses were still co-circulating in human population in China, while influenza A (H3N2) virus was predominant strain. The two antigenically and genetically distinguishable strains of influenza B virus were also still co-circulating in men in southern China. The antigenic analysis indicated that most of the H3N2 viruses were A/Panama/2007/99 (H3N2)-like strain, the most of the H1N1 viruses were antigenically similar to A/Beijing/262/95 (H1N1) virus. However, most of the influenza B viruses were B/Beijing/184/93-like strain, but few of them were antigenically similar to B/Shandong/7/97 virus. In the summer of 1998, the influenza outbreaks caused by H3N2 subtype of influenza A virus occurred widely in southern China. Afterwards, during 1998-1999 influenza season, a severe influenza epidemic caused by H3N2 virus emerged in northern China. The morbidity was reached as high as 10% in Beijing area. It was interesting that during influenza, surveillance from 1998 to 1999, five strains of avian influenza A (H9N2) virus were isolated from outpatients with influenza-like illness in July-August of 1998, and another one was repeatedly isolated from a child suffering from influenza-like disease in November of 1999 in Guangdong province. The genetic analysis revealed that the five strains isolated in 1998 were genetically closely related to H9N2 viruses being isolated from chickens (G9 lineage virus), whereas, A/Guangzhou/333/99 (H9N2) virus was a reassortant derived from reassortment between G9 and G1 lineage of avian influenza A (H9N2) viruses due to its genes encoding the HA, NA, NP and NS proteins, closely related to G9 lineage virus, the rest of the genes encoding the M and three polymerase (PB2, PB1 and PA) were closely related to G1 lineage strain of H9N2 virus. However, no avian influenza A (H5N1) virus has so far been isolated neither from in or outpatients with influenza-like disease in mainland China. Unfortunately, where did the reassortment occur and how did the reassortant transmit to men? These questions are still unknown.     

Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate

H9N2 subtype influenza A viruses have been identified in avian species worldwide and were isolated from humans in 1999, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. Reassortant H1N1 and H3N2 human influenza A viruses with the internal genes of the influenza A/Ann Arbor/6/60 (H2N2) (AA) cold-adapted (ca) virus have proven to be attenuated and safe as live virus vaccines in humans. Using classical genetic reassortment, we generated a reassortant virus (G9/AA ca) that contains the hemagglutinin and neuraminidase genes from influenza A/chicken/Hong Kong/G9/97 (H9N2) (G9) and six internal gene segments from the AA ca virus. When administered intranasally, the reassortant virus was immunogenic and protected mice from subsequent challenge with wild-type H9N2 viruses, although it was restricted in replication in the respiratory tract of mice. The G9/AA ca virus bears properties that are desirable in a vaccine for humans and is available for clinical evaluation and use, should the need arise.     

湖北省咸宁市2013－2017年流感监测结果分析

目的 对咸宁市流感样病例(influenza-like illness,ILI)标本进行病原学检测,分析流感流行趋势及病原学特点,为流感的防控提供科学依据。 方法 通过国家流感监测系统,收集2013－2017年度咸宁市中心医院流感样病例监测数据,采集流感样咽拭子标本,采用实时荧光定量PCR检测流感病毒核酸。 结果 2013－2017年共检测5 259份ILI标本,流感病毒核酸阳性595份,阳性率为11.31%;阳性率逐年攀升(χ²=102.733,P=0.000),2017年最高,达到17.88%;流感高发季以冬春季为主,间隔出现夏季高峰;流行型别主要是新甲型H1流感病毒、季节性H3流感病毒和B型流感病毒,2013年以新甲型H1为主,2016年以B型为主,2014-2015年和2017年以季节性H3为主;男女流感病毒阳性率差异无统计学意义;5～岁组阳性率最高,不同年龄组流感病毒核酸阳性率差异有统计学意义(χ²=61.624,P=0.000)。 结论 咸宁市在2013－2017年中流感以冬春季和夏季流行为主,流感病毒核酸阳性率呈现出逐年攀升的态势,新甲型H1、季节性H3、B型三种优势毒株交替出现,5～岁组儿童为发病高危人群。     

Human Case of Swine Influenza A (H1N1) Triple Reassortant Virus Infection, Wisconsin

Zoonotic infections with swine influenza A viruses are reported sporadically. Triple reassortant swine influenza viruses have been isolated from pigs in the United States since 1998. We report a human case of upper respiratory illness associated with swine influenza A (H1N1) triple reassortant virus infection that occurred during 2005 following exposure to freshly killed pigs.     

2017-2019年丽水市流感监测和甲型流感病毒HA基因进化分析

目的 对2017-2019年丽水市流行性感冒(简称流感)监测数据和甲型流感病毒HA基因进行分析,以了解丽水市流感的流行情况、病毒亚型构成和基因进化特征.方法 收集2017-2019年丽水市流感监测哨点医院的流感样病例(influenza-like illness,ILI)数据以及流感病毒病原学检测结果,采用描述性流行病...     

2003年广东省流感病毒的流行概况及特征

目的了解2003年广东省流感病毒的流行特点和抗原变异情况。方法根据广东地区流感监测资料进行分析；用交叉血凝抑制试验检测病毒的抗原性；用逆转录-聚合酶链反应扩增病毒HA1基因，纯化产物进行核苷酸序列测定。将序列和Genebank中相关序列进行比较，用MegAlign软件绘制种系发生树。结果全年分离到510株流感病毒，其中H3N2亚型流感481株，占92．4％；乙型流感29株，占7．6％。实验室证实流感爆发52起，其中50起暴发是由H3N2亚型流感病毒引起，2起暴发是由乙型流感病毒引起。H3N2亚型流感病毒抗原性和疫苗侏A／Panama／2007／99（H3N2）有所不同。类似干A／Fujian／411／02（H3N2）。在HAl区氨基酸序列上，和疫苗株A／Panama／2007／99（H3N2）同源性为92．1％，存在有25个氨基酸差异。28株乙型流感病毒属于Victoria系，抗原性类似疫苗侏B／HongKong／330／01，1株乙型病毒属于Yamagata系，抗原性不同干B／sichuan／379／99。结论2003年广东省流感活动比2002年要强；同时流行着甲型（H3N2）和2个谱系的乙型流感病毒，H3N2亚型毒侏是优势侏，抗原性发生了漂移。     

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1).     

上海市金山区2015—2019年流感病原学监测结果分析

目的 了解金山区2015—2019监测年度流行性感冒(流感)的病原学特征,为流感防控提供科学依据。 方法 收集金山区2015—2019监测年度流感样病例的鼻咽拭子标本,通过Real-time RT-PCR鉴定流感病毒亚型,核酸阳性标本用马丁达比犬肾 (Madin-Darby canine kidney, MDCK)细胞和(或)无特定病原体(specific pathogen free, SPF)鸡胚分离培养,对甲型流感进行HA基因分析。 结果 2015—2019监测年度共采集流感样病例鼻咽拭标本4 263份,流感病毒核酸检测总阳性率为23.95%(1 021/4 263)。其中甲型流感病毒检出阳性数占检测总阳性数的80.99%,主要为甲型H3N2和甲型H1N1。流感病毒检出阳性率及分型情况呈季节分布,各年龄组核酸检测阳性率差异有统计学意义(χ²=83.783,P<0.05),其中60岁以上组阳性率最高30.77%,0～岁组阳性率最低12.10%,不同性别间流感病毒核酸检测阳性率差异无统计学意义(χ²=3.740,P>0.05)。基因进化分析表明金山区甲型H1N1和H3N2流感病毒与疫苗推荐株亲缘性较近,但与国内近几年分离到的甲型流感毒株比较,甲型H1N1和甲型H3N2流感病毒HA基因均存在一定的变异。 结论 金山区2015—2019年以甲型流感病毒株流行为主。目前的流感疫苗对甲型流感病毒具有预防作用,但不同年份流感病毒HA基因存在一定的变异,应加强流感病毒监测,及时发现病毒的变异情况,提高疫苗的保护作用。     

Update: Influenza A (H3N2)v transmission and guidelines - five states, 2011

From August 17 to December 23, 2011, CDC received reports of 12 human infections with influenza A (H3N2)v viruses that have the matrix (M) gene from the influenza A (H1N1)pdm09 virus (formerly called swine-origin influenza A [H3N2] and pandemic influenza A [H1N1] 2009 viruses, respectively). The 12 cases occurred in five states (Indiana, Iowa, Maine, Pennsylvania, and West Virginia), and 11 were in children. Six of the 12 patients had no identified recent exposure to swine. Three of the 12 patients were hospitalized, and all have recovered fully.