H6N6亚型禽流感病毒进化演变及跨种属传播研究进展

H6N6亚型禽流感病毒(AVI)在欧亚大陆野生鸟类和家禽中广泛流行,通过适应性突变和基因重配,其宿主范围逐渐扩大,遗传分析表明该病毒是高致病禽流感病毒H5N6的先祖之一。近年来研究证实,H6N6亚型AIV可以感染小鼠、雪雕、猪等哺乳动物,甚至在健康人群中检测到H6亚型AIV的血清特异性抗体,表明H6N6亚型禽流感病毒具有跨越物种屏障感染哺乳动物的能力,并对人类健康构成潜在威胁。本文从H6N6病毒起源、流行情况、进化演变及跨种属传播的研究进展进行综述,以期为H6N6亚型AIV的防控提供参考。     

新疆首例人感染H7N9禽流感病例流行病学调查

目的分析新疆首例人感染H7N9禽流感病例流行病学特征,探讨该病例可能的感染来源,为新疆制定人感染H7N9禽流感防控措施提供依据。方法对一例不明原因肺炎病例展开现场流行病学调查,在病原学排查的同时对病例及其密切接触者和可疑感染来源进行流行病学调查,采集相关标本送实验室检测,并应用描述流行病学方法进行分析。结果该病例有明确的禽类养殖及无防护措施的禽排泄物及其污染环境暴露史,呼吸道标本检测出人感染H7N9禽流感病毒,相关外环境和家禽标本H7N9禽流感病毒核酸检测阳性,环境标本分离禽流感病毒与人标本中分离的禽流感病毒HA片段和NA片段同源性为99.9%和100.0%,未发现人与人之间传播病例。结论该病例为新疆确诊的首例人感染H7N9禽流感病例,传播途径可能为禽—环境—人或者禽—人;加强门诊医生诊断敏感性和强化不明原因肺炎监测工作是及时发现与处理人感染H7N9禽流感疫情的重要手段。     

H7N9型禽流感诊疗方案及日常预防

诊疗方案中国国家卫生和计划生育委员会2013年3月3日印发人感染H7N9禽流感诊疗方案、防控方案及医院感染预防与控制技术指南。根据人感染H7N9禽流感诊疗方案(2013年第1版),人感染H7N9禽流感传染源目前尚不明确,根据以往经验及本次病例流行病学调查,推测可能为携带H7N9禽流感病毒的禽类及其分泌物或排泄物。     

人禽流感诊疗方案（2005版）

人禽流行性感冒（以下称人禽流感）是由禽甲型流感病毒某些亚型中的一些毒株引起的急性呼吸道传染病.早在1981年,美国即有禽流感病毒H7N7 感染人类引起结膜炎的报道.1997年,我国香港特别行政区发生H5N1型人禽流感,导致6人死亡,在世界范围内引起了广泛关注.近年来,人们又先后获得了H9N2、H7N2、H7N3亚型禽流感病毒感染人类的证据,荷兰、越南、泰国、柬埔寨等国家相继出现了人禽流感病例.尽管目前人禽流感只是呈地区性小规模流行,但是,考虑到人类对禽流感病毒普遍缺乏免疫力以及人类感染H5N1型禽流感病毒后的高病死率,WHO认为该疾病可能是对人类存在潜在威胁最大的疾病之一。     

何谓H7N9禽流感——应正确认识和积极防治

H7N9型禽流感（H7N9 avian influenza）是一种新型禽流感病毒引起,并且可导致人类感染,于2013年3月31日在中国上海和安徽两地率先报告。     

广东两株人禽流感H5N1毒株节段基因及蛋白特征和进化分析

禽流感病毒(AIV)毒株是感染禽类和人类的重要病原体,感染人类可引起急性呼吸道传染病.目前常见的亚型有H5N1、H7N7和H9N2,其中以H5N1毒性最强[1].自1997年3月,禽流感H5N1毒株初次感染人类以来.截至2011年1月5日,全球共有15个国家出现感染人禽流感H5N1病毒的病例,横跨亚、非大陆,确诊病例534例,死亡312例,病死率为58.4%[2].其病死率在急性传染病中已名列前茅.广东地区的首例人禽流感患者于2006年2月24日出现在广州市,死于2006年3月2日.     

H7N9禽流感病毒

禽流感病毒通常在鸟类中传播。虽然偶尔发现某些H7禽病毒（H7N2、H7N3和H7N7）感染人类,但直到2013年3月中国报告人感染H7N9禽流感病毒病例之前,没有人类感染该病毒的报告。截止2014年5月,感染这一病毒的大多数病人出现了重症肺炎。常见症状包括：发热、咳嗽和呼吸急促。据我们所知,仅有少数患者出现流感样症状后,在未就医的情况下痊愈。     

人禽流感诊疗方案(2005版)

人禽流行性感冒(以下称人禽流感)是由禽甲型流感病毒某些亚型中的一些毒株引起的急性呼吸道传染病。早在1981年,美国即有禽流感病毒H7N7感染人类引起结膜炎的报道。1997年,我国香港特别行政区发生H5N1型人禽流感,导致6人死亡,在世界范围内引起了广泛关注。近年来,人们又先后获得了H9N2、H7N2、H7N3亚型禽流感病毒感染人类的证据,荷兰、越南、泰国、柬埔寨等国家相继出现了人禽流感病例。尽管目前人禽流感只是呈地区性小规模流行,但是,考虑到人类对禽流感病毒普遍缺乏免疫力以及人类感染H5N1型禽流感病毒后的高病死率,WHO认为该疾病可…     

H4亚型禽流感病毒的流行与进化

禽流感是一种主要感染禽类且部分具有感染哺乳动物能力的传染病。禽流感病毒亚型众多,流行广泛,给人类生产生活带来极大影响。随着低致病性禽流感感染人事件的增多,低致病性禽流感病毒逐渐引起公众的关注。H4禽流感病毒作为低致病性禽流感的优势亚型,毒株数量众多且分布地区广泛,但受到的关注以及研究较少,相关研究多为进化和分子生物学特征分析,公众对其认知有限。为了更好的了解H4亚型AIV的流行与进化,探讨其致病、跨种传播潜力,明确H4亚型AIV的潜在公共卫生风险。本文论述了H4亚型AIV的流行、宿主感染分布、病毒的进化与变异,围绕其变异潜力和致病力增强现状进行归纳分析,以期提高公众对LPAIV的认知,为H4亚型AIV综合防控提供科学依据。     

近期中国禽流感病毒的流行病学调查及其演变

正禽流感病毒(AIVs)通常具有种属特异性,感染宿主主要限于禽类。流行范围较广,值得注意的是其很少发生跨种传播感染人类和其他哺乳动物。1中国过去爆发的禽流感疫情及流行病学调查亚洲的第一株H9N2低致病性禽流感病毒(LPAIV)和H5N1高致病性禽流感病毒(HPAIV)分别于1994年和1996年分离自中国广东省。2013年3月     

Quantification of the effect of vaccination on transmission of avian influenza (H7N7) in chickens

Recent outbreaks of highly pathogenic avian influenza (HPAI) viruses in poultry and their threatening zoonotic consequences emphasize the need for effective control measures. Although vaccination of poultry against avian influenza provides a potentially attractive control measure, little is known about the effect of vaccination on epidemiologically relevant parameters, such as transmissibility and the infectious period. We used transmission experiments to study the effect of vaccination on the transmission characteristics of HPAI A/Chicken/Netherlands/03 H7N7 in chickens. In the experiments, a number of infected and uninfected chickens is housed together and the infection chain is monitored by virus isolation and serology. Analysis is based on a stochastic susceptible, latently infected, infectious, recovered (SEIR) epidemic model. We found that vaccination is able to reduce the transmission level to such an extent that a major outbreak is prevented, important variables being the type of vaccine (H7N1 or H7N3) and the moment of challenge after vaccination. Two weeks after vaccination, both vaccines completely block transmission. One week after vaccination, the H7N1 vaccine is better than the H7N3 vaccine at reducing the spread of the H7N7 virus. We discuss the implications of these findings for the use of vaccination programs in poultry and the value of transmission experiments in the process of choosing vaccine.     

Antigenic Evolution Characteristics and Immunological Evaluation of H9N2 Avian Influenza Viruses from 1994–2019 in China

The H9N2 subtype avian influenza viruses (AIVs) have been circulating in China for more than 20 years, attracting more and more attention due to the potential threat of them. At present, vaccination is a common prevention and control strategy in poultry farms, but as virus antigenicity evolves, the immune protection efficiency of vaccines has constantly been challenged. In this study, we downloaded the hemagglutinin (HA) protein sequences of the H9N2 subtype AIVs from 1994 to 2019 in China—with a total of 5138 sequences. The above sequences were analyzed in terms of time and space, and it was found that h9.4.2.5 was the most popular in various regions of China. Furthermore, the prevalence of H9N2 subtype AIVs in China around 2006 was different. The domestic epidemic branch was relatively diversified from 1994 to 2006. After 2006, the epidemic branch each year was h9.4.2.5. We compared the sequences around 2006 as a whole and screened out 15 different amino acid positions. Based on the HA protein of A/chicken/Guangxi/55/2005 (GX55), the abovementioned amino acid mutations were completed. According to the 12-plasmid reverse genetic system, the rescue of the mutant virus was completed using A/PuertoRico/8/1934 (H1N1) (PR8) as the backbone. The cross hemagglutination inhibition test showed that these mutant sites could transform the parental strain from the old to the new antigenic region. Animal experiments indicated that the mutant virus provided significant protection against the virus from the new antigenic region. This study revealed the antigenic evolution of H9N2 subtype AIVs in China. At the same time, it provided an experimental basis for the development of new vaccines.     

Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease

Avian influenza viruses of the H5 and H7 hemagglutinin subtypes, and Newcastle disease virus (NDV), are important pathogens in poultry worldwide. Specifically, the highly pathogenic H5N1 avian influenza virus is a particular threat because it has now occurred in more than 40 countries on several continents. Inasmuch as most chickens worldwide are vaccinated with a live NDV vaccine, we embarked on the development of vaccine prototypes that would have dual specificity and would allow a single immunization against both avian influenza and Newcastle disease. Using reverse genetics, we constructed a chimeric avian influenza virus that expressed the ectodomain of the hemagglutinin-neuraminidase gene of NDV instead of the neuraminidase protein of the H5N1 avian influenza virus. Our second approach to creating a bivalent vaccine was based on expressing the ectodomain of an H7 avian influenza virus hemagglutinin in a fusogenic and attenuated NDV background. The insertion into the NDV genome of the foreign gene (containing only its ectodomain, with the transmembrane and cytoplasmic domains derived from the F protein of NDV) resulted in a chimeric virus with enhanced incorporation of the foreign protein into virus particles. A single immunization of chickens with this improved vaccine prototype virus induced not only a 90% protection against an H7N7 highly pathogenic avian influenza virus, but also complete immunity against a highly virulent NDV. We propose that chimeric constructs should be developed for convenient, affordable, and effective vaccination against avian influenza and Newcastle disease in chickens and other poultry.     

2014-2019年中山市H9亚型禽流感监测及病例特征分析

目的 分析中山市H9亚型禽流感病毒外环境监测情况及人感染H9N2禽流感病例特征,指导H9N2禽流感防控工作.方法 2014-2019年采集监测镇区内的禽类批发市场、活禽销售市场和生鲜禽销售市场3类交易场所的外环境标本进行禽流感病毒核酸检测,并对人感染H9N2禽流感报告病例进行流行病学分析.结果 共采集和检测外环境标本9...     

Avian influenza virus infections in humans

Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The epidemiology, virology, clinical features, laboratory diagnosis, management, and hospital infection control measures are reviewed from a clinical perspective.     

Virus Adaptation Following Experimental Infection of Chickens with a Domestic Duck Low Pathogenic Avian Influenza Isolate from the 2017 USA H7N9 Outbreak Identifies Polymorphic Mutations in Multiple Gene Segments

In March 2017, highly pathogenic (HP) and low pathogenic (LP) avian influenza virus (AIV) subtype H7N9 were detected from poultry farms and backyard birds in several states in the southeast United States. Because interspecies transmission is a known mechanism for evolution of AIVs, we sought to characterize infection and transmission of a domestic duck-origin H7N9 LPAIV in chickens and genetically compare the viruses replicating in the chickens to the original H7N9 clinical field samples used as inoculum. The results of the experimental infection demonstrated virus replication and transmission in chickens, with overt clinical signs of disease and shedding through both oral and cloacal routes. Unexpectedly, higher levels of virus shedding were observed in some cloacal swabs. Next generation sequencing (NGS) analysis identified numerous non-synonymous mutations at the consensus level in the polymerase genes (i.e., PA, PB1, and PB2) and the hemagglutinin (HA) receptor binding site in viruses recovered from chickens, indicating possible virus adaptation in the new host. For comparison, NGS analysis of clinical samples obtained from duck specimen collected during the outbreak indicated three polymorphic sides in the M1 segment and a minor population of viruses carrying the D139N (21.4%) substitution in the NS1 segment. Interestingly, at consensus level, A/duck/Alabama (H7N9) had isoleucine at position 105 in NP protein, similar to HPAIV (H7N9) but not to LPAIV (H7N9) isolated from the same 2017 influenza outbreak in the US. Taken together, this work demonstrates that the H7N9 viruses could readily jump between avian species, which may have contributed to the evolution of the virus and its spread in the region.     

Genetic Characterization and Pathogenicity of H7N7 and H7N9 Avian Influenza Viruses Isolated from South Korea

H7 low pathogenic avian influenza viruses (LPAIVs) can mutate into highly pathogenic avian influenza viruses (HPAIVs). In addition to avian species, H7 avian influenza viruses (AIVs) also infect humans. In this study, two AIVs, H7N9 (20X-20) and H7N7 (34X-2), isolated from the feces of wild birds in South Korea in 2021, were genetically analyzed. The HA cleavage site of the two H7 Korean viruses was confirmed to be ELPKGR/GLF, indicating they are LPAIVs. There were no amino acid substitutions at the receptor-binding site of the HA gene of two H7 Korean viruses compared to that of A/Anhui/1/2013 (H7N9), which prefer human receptors. In the phylogenetic tree analysis, the HA gene of the two H7 Korean viruses shared the highest nucleotide similarity with the Korean H7 subtype AIVs. In addition, the HA gene of the two H7 Korean viruses showed high nucleotide similarity to that of the A/Jiangsu/1/2018(H7N4) virus, which is a human influenza virus originating from avian influenza virus. Most internal genes (PB2, PB1, PA, NP, NA, M, and NS) of the two H7 Korean viruses belonged to the Eurasian lineage, except for the M gene of 34X-2. This result suggests that active reassortment occurred among AIVs. In pathogenicity studies of mice, the two H7 Korean viruses replicated in the lungs of mice. In addition, the body weight of mice infected with 34X-2 decreased 7 days post-infection (dpi) and inflammation was observed in the peribronchiolar and perivascular regions of the lungs of mice. These results suggest that mammals can be infected with the two H7 Korean AIVs. Our data showed that even low pathogenic H7 AIVs may infect mammals, including humans, as confirmed by the A/Jiangsu/1/2018(H7N4) virus. Therefore, continuous monitoring and pathogenicity assessment of AIVs, even of LPAIVs, are required.     

Characterization of H9N2 Avian Influenza Viruses Isolated from Poultry Products in a Mouse Model

Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are not yet enzootic; however, avian influenza viruses, including H5N1, H7N9, H5N6, and H9N2, have been repeatedly detected in raw poultry meat carried by international flight passengers from Asian countries to Japan. Although H9N2 virus-contaminated poultry products intercepted by the animal quarantine service at the Japan border have been characterized in chickens and ducks, the biological properties of those H9N2 viruses in mammals remain unclear. Here, we characterized the biological features of two H9N2 virus isolates [A/chicken/Japan/AQ-HE28-50/2016 (Ck/HE28-50) and A/chicken/Japan/AQ-HE28-57/2016 (Ck/HE28-57)] in a mouse model. We found that these H9N2 viruses replicate well in the respiratory tract of infected mice without adaptation, and that Ck/HE28-57 caused body weight loss in the infected mice. Our results indicate that H9N2 avian influenza viruses isolated from raw chicken meat products illegally brought to Japan can potentially infect and cause disease in mammals.     

Spatiotemporal Associations and Molecular Evolution of Highly Pathogenic Avian Influenza A H7N9 Virus in China from 2017 to 2021

Highly pathogenic (HP) H7N9 avian influenza virus (AIV) emerged in China in 2016. HP H7N9 AIV caused at least 33 human infections and has been circulating in poultry farms continuously since wave 5. The genetic divergence, geographic patterns, and hemagglutinin adaptive and parallel molecular evolution of HP H7N9 AIV in China since 2017 are still unclear. Here, 10 new strains of HP H7N9 AIVs from October 2019 to April 2021 were sequenced. We found that HP H7N9 was primarily circulating in Northern China, particularly in the provinces surrounding the Bohai Sea (Liaoning, Hebei, and Shandong) since wave 6. Of note, HP H7N9 AIV phylogenies exhibit a geographical structure compatible with high levels of local transmission after unidirectional rapid geographical expansion towards the north of China in 2017. In addition, we showed that two major subclades were continually expanding with the viral population size undergoing a sharp increase after 2018 with an obvious seasonal tendency. Notably, the hemagglutinin gene showed signs of parallel evolution and positive selection. Our research sheds light on the current epidemiology, evolution, and diversity of HP H7N9 AIV that can help prevent and control the spreading of HP H7N9 AIV.     

Pathogenicity and transmissibility of three avian influenza A (H5N6) viruses isolated from wild birds

Since 2013, highly pathogenic H5N6 avian influenza viruses (AIVs) have emerged in poultry and caused sporadic human infections in Asia. The recent discovery of three new avian H5N6 viruses – A/oriental magpie-robin/Guangdong/SW8/2014 (H5N6), A/common moorhen/Guangdong/GZ174/2014 (H5N6) and A/Pallas's sandgrouse/Guangdong/ZH283/2015 (H5N6) – isolated from apparently healthy wild birds in Southern China in 2014–2015 raises great concern for the spread of these highly pathogenic AIVs (HPAIVs) and their potential threat to human and animal health. In our study, we conducted animal experiments and tested their pathogenicity in ducks, chickens and mice. Ducks can carry and shed the H5N6 HPAIVs, but show no ill effects. On the other hand, these H5N6 HPAIVs can efficiently infect, transmit and cause death in chickens. Due to the overlap of habitats, domestic ducks play an important role in circulating AIVs between poultry and wild birds. Our results raise the possibility that wild birds disseminate these H5N6 HPAIVs to poultry along their flyways and thus pose a great threat to the poultry industry. These viruses are also highly pathogenic to mice, suggesting they pose a potential threat to mammals and, thus, public health. One virus isolated in 2015 replicates much more efficiently and is more lethal in these animals than the two other viruses isolated in 2014. It seems that the H5N6 viruses tend to be more lethal as time passes. Therefore, it is necessary to vigilantly monitor H5N6 HPAIVs in wild birds and poultry.