H7N9

H7N9

·編者按·

H7N9（influenza A virus subtype H7N9）屬甲型流感病毒，是禽流感病毒的一個(gè)亞型。2013年3月，我國(guó)上海和安徽兩地首先確診H7N9禽流感病毒感染人的病例。此后，中國(guó)大陸其他地區(qū)、中國(guó)香港、中國(guó)臺(tái)灣以及東南亞部分國(guó)家也發(fā)現(xiàn)了H7N9禽流感病毒感染人的病例，引起全球關(guān)注。國(guó)內(nèi)外生物學(xué)家分析發(fā)現(xiàn)新型H7N9禽流感病毒起源于候鳥和家禽的多個(gè)基因重配，其中HA基因與華東地區(qū)家鴨群的H7N3病毒遺傳關(guān)系最近，NA基因與2010/11香港地區(qū)的遷徙候鳥中分離到的（H11N9和H2N9）基因遺傳關(guān)系最近，另外6個(gè)內(nèi)部基因均來源于中國(guó)家禽中H9N2。H7亞型與當(dāng)?shù)夭煌拗鞯腍9N2病毒經(jīng)過多次重組產(chǎn)生了新型H9N2，從水禽（家鴨）傳遞到陸生家禽（雞、鵪鶉、鴿子等）體內(nèi)。

截至目前，H7N9禽流感病毒感染人的病例仍以散發(fā)形式存在。目前已有H7N9禽流感病毒滅活疫苗、減毒活疫苗、重組疫苗完成了一期或二期臨床研究，但距離疫苗獲批使用尚有一段距離。

本專題得到趙衛(wèi)教授（南方醫(yī)科大學(xué)）的大力支持。

·熱點(diǎn)數(shù)據(jù)排行·

截至2017年2月14日，中國(guó)知網(wǎng)（CNKI）和Web of Science（WOS）的數(shù)據(jù)報(bào)告顯示，以“H7N9”為詞條可以檢索到的期刊文獻(xiàn)分別為1446、941條，本專題將相關(guān)數(shù)據(jù)按照：研究機(jī)構(gòu)發(fā)文數(shù)、作者發(fā)文數(shù)、期刊發(fā)文數(shù)、被引用頻次進(jìn)行排行，結(jié)果如下。

研究機(jī)構(gòu)發(fā)文數(shù)量排名（CNKI）

研究機(jī)構(gòu)發(fā)文數(shù)量排名（WOS）

作者發(fā)文數(shù)量排名（CNKI）

作者發(fā)文數(shù)量排名（WOS）

作者發(fā)文數(shù)量排名（CNKI）（續(xù)表）

作者發(fā)文數(shù)量排名（WOS）（續(xù)表）

期刊發(fā)文數(shù)量排名（CNKI）

期刊發(fā)文數(shù)量排名（WOS）

（數(shù)據(jù)來源：中國(guó)知網(wǎng)、Web of Science，檢索時(shí)間：2017-02-14）

根據(jù)中國(guó)知網(wǎng)（CNKI）數(shù)據(jù)報(bào)告，以“H7N9”等為詞條可以檢索到的高被引論文排行結(jié)果如下。

國(guó)內(nèi)數(shù)據(jù)庫高被引論文排行

根據(jù)Web of Science統(tǒng)計(jì)數(shù)據(jù)，以“H7N9”為詞條可以檢索到的高被引論文排行結(jié)果如下。

國(guó)外數(shù)據(jù)庫高被引論文排行

·經(jīng)典文獻(xiàn)推薦·

基于Web of Science檢索結(jié)果，利用Histcite軟件選取LCS（Local Citation Score，本地引用次數(shù)）TOP 50文獻(xiàn)作為節(jié)點(diǎn)進(jìn)行分析，得到本領(lǐng)域推薦的經(jīng)典文獻(xiàn)如下。

本領(lǐng)域經(jīng)典文獻(xiàn)

Human infection with a novel avian-origin influenza A (H7N9) virus

Gao, RB; Cao, B; Hu, YW; et al.

Background: Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avianorigin influenza A (H7N9) virus. Methods: We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. Results: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin

(HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. Conclusions: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients.

來源出版物：New England Journal of Medicine, 2013, 368(20): 1888-1897

Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: Phylogenetic, structural, and coalescent analyses

Liu, D; Shi, WF; Shi, Y; et al.

Abstract: Background: On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogeneticand coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events. Methods: We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties. Findings: The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades. Interpretation: The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic- poultry-toperson transmission should be closely watched in the future.

來源出版物：The Lancet, 2013, 381(9881): 1926-1932

H7N9 influenza viruses are transmissible in ferrets by respiratory droplet

Zhang, QY; Shi, JZ; Deng, GH; et al.

Abstract: A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in China since 18 February 2013. Control measures in H7N9 virus-positive live poultry markets have reduced the number of infections; however, the character of the virus, including its pandemic potential, remains largely unknown. We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice. Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplet. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.

來源出版物：Science, 2013, 341(6144): 410-414

Biological features of novel avian influenza A (H7N9) virus

Zhou, JF; Wang, DY; Gao, RB

Abstract: Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently inex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.

來源出版物：Nature, 2013, 499(7459): 500-503

The genesis and source of the H7N9 influenza viruses causing human infections in China

Lam, TTY; Wang, J; Shen, YY; et al.

Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths(1,2). Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic(1,3,4). However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known(5). Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

來源出版物：Nature, 2013, 502(7470): 241-244