·推薦論文摘要·

具有常數(shù)輸入的H7N9禽流感動力學模型分析

郭樹敏，李學志

研究了新型的禽流感病毒傳播的禽類-人類動力學模型。在有染病禽類輸入和無染病禽類輸入兩種情況下，得到了系統(tǒng)的平衡點的存在性與基本再生數(shù)，并給出了系統(tǒng)的無病平衡點和地方病平衡點的穩(wěn)定性條件。

H7N9禽流感；動力學模型；基本再生數(shù)；穩(wěn)定性

來源出版物：信陽師范學院學報（自然科學版）, 2017, 30(1): 13-16

聯(lián)系郵箱：郭樹敏，shuminguo123456@ 126.com

人用H7N9禽流感疫苗的研究進展

郭琦，廖國陽

摘要：2013年初，中國部分城市和地區(qū)出現(xiàn)了禽流感病毒H7N9感染人的病例，截止目前已有超過500人感染H7N9，感染者死亡率約為30%。WHO專家預測，禽流感病毒H7N9可能引起大流行。因此，人用H7N9禽流感疫苗的研發(fā)刻不容緩。目前已有多個H7N9疫苗備選株通過了WHO安全性評價，可用于疫苗研發(fā)。在此基礎上，H7N9滅活疫苗、減毒活疫苗以及重組疫苗均已取得較好的研究結果。本文對人用H7N9禽流感疫苗的研究進展作一綜述。

關鍵詞：流感病毒；H7N9；疫苗

來源出版物：中國生物制品學雜志, 2017, 30(2): 210-214

聯(lián)系郵箱：廖國陽，liaogy@imbcams.com.cn

重組H7N9亞型流感病毒血凝素（HA）的表達及鑒定

孟令楠，任志廣，冀顯亮，等

摘要：目的：為了獲得H7N9HA蛋白，利用昆蟲桿狀病毒表達系統(tǒng)表達了H7N9HA基因并獲得重組H7N9亞型流感病毒HA蛋白。方法：將H7N9亞型流感病毒的HA蛋白基因擴增并克隆到pFastBacⅠ載體中，構建重組穿梭質(zhì)粒，轉(zhuǎn)染昆蟲sf9細胞后獲得重組桿狀病毒，對大量培養(yǎng)后表達的H7N9HA蛋白進行SDS-PAGE、Western blot和間接免疫熒光檢測。分別在0 d和14 d用純化的表達產(chǎn)物HA蛋白免疫小鼠。結果：測序鑒定重組表達載體構建正確；SDS-PAGE顯示純化的表達蛋白分子質(zhì)量為67 ku；Western blot分析該蛋白能夠被雞抗流感病毒IgG識別；雞抗流感病毒抗體間接免疫熒光法測定HA蛋白的表達，在感染HA的昆蟲細胞中出現(xiàn)特異性熒光。結論：成功的表達了H7N9的HA蛋白，并且此HA蛋白能成功的誘導小鼠體內(nèi)的免疫反應，并起到良好的保護作用。

關鍵詞：流感病毒；H7N9HA蛋白；桿狀病毒表達系統(tǒng)

來源出版物：中國病原生物學雜志, 2016, 11(5): 401-410

聯(lián)系郵箱：夏咸柱，xiaxzh@cae.cn

2013—2014年浙江省武義縣職業(yè)暴露人群及外環(huán)境H7N9禽流感病毒監(jiān)測分析

王曉柳，饒國強，程曉呤，等

摘要：目的：探討H7N9禽流感的來源及高危因素，為制定科學的防控策略及流感流行預警提供依據(jù)。方法：采集2013—2014年浙江省武義縣從事銷售和屠宰家禽的職業(yè)暴露人群血清標本43份，采用血凝抑制實驗檢測禽流感病毒抗體；采集外環(huán)境標本375份，采用實時熒光定量聚合酶鏈反應方法檢測H7N9禽流感病毒核酸，對監(jiān)測結果進行分析。結果：職業(yè)暴露人群H7N9禽流感病毒抗體均為陰性，2014年有6個監(jiān)測場所檢出H7N9禽流感病毒陽性，陽性率為11.11%（6/54），陽性場所分布在3個鄉(xiāng)鎮(zhèn)。家禽糞便標本、籠具表面涂抹物等標本檢出陽性10份，陽性率2.67%（10/375）。結論：武義縣禽流感職業(yè)暴露人群尚未發(fā)現(xiàn)禽流感隱性感染者，在武義縣3家活禽和宰殺市場的外環(huán)境中檢測到H7N9禽流感病毒，提示存在人感染H7N9禽流感病毒的風險。

關鍵詞：職業(yè)暴露；外環(huán)境；H7N9禽流感；監(jiān)測

來源出版物：實用預防醫(yī)學, 2016, 23(6): 712-714

聯(lián)系郵箱：王曉柳，253525754@qq.com

2014年9—12月中國內(nèi)地人感染H7N9禽流感疫情流行病學特征分析

周蕾，任瑞琦，張彥平，等

摘要：目的：分析中國大陸地區(qū)2014年9—12月人感染H7N9禽流感疫情情況，為防控策略的制定和調(diào)整提供科學依據(jù)。方法：以我國報告的確診H7N9禽流感病例為研究對象，用描述性流行病學方法分析病例的時間、空間和人群分布特點。結果：2014年9—12月，我國共確診人感染H7N9禽流感病例31例，死亡9例，病例數(shù)較上年同期增長2.1倍。病例分布在7個省（直轄市），其中13例發(fā)生在既往有疫情的縣（區(qū)），18例發(fā)生在新發(fā)縣（區(qū)）。病例的年齡中位數(shù)為54歲（7～83歲），男性占48%（15/31）。93.5%的病例在發(fā)病前有禽類相關暴露史。結論：近期中國內(nèi)地人感染H7N9禽流感疫情較去年同期明顯增長，部分省份出現(xiàn)地域聚集性，多數(shù)病例在發(fā)病前有活禽或活禽市場暴露史。近期疫情仍會呈現(xiàn)散發(fā)態(tài)勢，仍會繼續(xù)出現(xiàn)新發(fā)病例和新發(fā)省份或地區(qū)，減少禽類或活禽市場暴露仍是防控重點。

關鍵詞：人感染H7N9禽流感；流行病學特征；疫情形勢

來源出版物：疾病監(jiān)測, 2015, 30(4): 265-268

聯(lián)系郵箱：李群，liqun@chinacdc.cn

來源出版物：Epidemiology and Infection, 2017, 145(1):

133-140

聯(lián)系郵箱：Chen, EF; enfchen@163.com

Estimating risks of inapparent avian exposure for human infection: Avian influenza virus A (H7N9) in Zhejiang Province, China

Ge, E; Zhang, RJ; Li, DK; et al.

Abstract: Inapparent avian exposure was suspected for the sporadic infection of avian influenza A (H7N9) occurring in China. This type of exposure is usually unnoticed and difficult to model and measure. Infected poultry with avian influenza H7N9 virus typically remains asymptomatic, which may facilitate infection through inapparent poultry/bird exposure, especially in a country with widespread practice of backyard poultry. The present study proposed a novel approach that integrated ecological and case-control methods to quantify the risk of inapparent avian exposure on human H7N9 infection. Significant associations of the infection with chicken and goose densities, but not with duck density, were identified after adjusting for spatial clustering effects of the H7N9 cases across multiple geographic scales of neighborhood, community, district and city levels. These exposure risks varied geographically in association with proximity to rivers and lakes that were also proxies for inapparent exposure to avian-related environment. Males, elderly people, and farmers were high-risk subgroups for the virus infection. These findings enable health officials to target educational programs and awareness training in specific locations to reduce the risks of inapparent exposure.

來源出版物：Scientific Reports, 2017, 7: 40016

聯(lián)系郵箱：Wei, XL; xiaolin.wei@utoronto.ca

In vitro exposure system for study of aerosolized influenza virus

Creager, HM; Zeng, H; Pulit-Penaloza, JA; et al.

Abstract: Infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. To better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. Procedures for cellular infection and calculation of exposure dose were developed and tested using viruses characterized by distincttransmission and pathogenicity phenotypes: an HPAI H5N1, an LPAI H7N9, and a seasonal H3N2 virus. While all three aerosolized viruses were highly infectious in a human bronchial epithelial cell line (Calu-3) cultured submerged in media, differences between the viruses were observed in primary human alveolar epithelial cells and in Calu-3 cells cultured at air-liquid interface. This system provides a novel enhancement to traditional in vitro experiments, particularly those focused on the early stages of infection.

關鍵詞：influenza; aerosols; cell culture; viral replication; avian viruses

來源出版物：Virology, 2017, 500: 62-70

聯(lián)系郵箱：Belser, JA; jax6@cdc.gov

Susceptibility of chickens, quail, and pigeons to an H7N9 human influenza virus and subsequent egg-passaged strains

Uchida, Y; Kanehira, K; Takemae, N; et al.

Abstract: H7N9 human influenza virus A/Anhui/1/2013 (Anhui2013) showed low pathogenicity in chickens, quail, and pigeons, with quail being the most susceptible among the species tested. IVPIE1-1, which was recovered from a dead chicken after intravenous inoculation of Anhui 2013, had broader tissue tropism in chickens than did the original inoculum, as well as amino acid substitutions in the polymerase acidic gene and neuraminidase gene segments, but its pathogenicity was not enhanced. Viruses obtained after passage of Anhui 2013 in 10-and 14-day-old embryonated eggs showed rapid accumulation of amino acid substitutions at the receptor-binding site of the hemagglutinin protein. Two strains obtained through egg passage, 10E4/14E17 and 10E4/10E13, replicated better in intranasally infected chickens than did the original Anhui 2013 strain, yet the new isolates showed low pathogenicity in chickens despite their amino acid substitutions. The increased virus replication in chickens of 10E4/14E17 and 10E4/10E13 was not correlated with temperature-sensitive replication, given that virus replication was suppressed at increased temperatures. The existence of highly susceptible hosts, such as quail, which permit asymptomatic infection, facilitates increased mutation of the virus through amino acid substitution at the receptor-binding site, and this might be one of the mechanisms underlying the prolonged circulation of H7N9 influenza virus.

來源出版物：Archives of Virology, 2017, 162 (1): 103-116

聯(lián)系郵箱：Saito, T; uchiyu@affrc.go.jp

PB2 substitutions V598T/I increase the virulence of H7N9 influenza A virus in mammals

Hu, M; Yuan, SF; Zhang, K; et al.

Abstract: PB2 is one of the subunits of the influenza A virus (IAV) polymerase complex. By bioinformatics analysis we identified PB2 substitutions at positions 389 and 598 among IAV isolates from humans, which might associate with viral pathogenicity. To evaluate the biological significance of these substitutions, PB2-K389R and -V598T/I mutant viruses of avian H7N9 IAVs were generated by reverse genetics. Compared to the wild type, the mutant viruses displayed an enhanced growth capacity in human and mammalian cells. Meanwhile, they presented increased transcription and replication by producing higher levels of viral mRNA, cRNA and vRNA. Minireplicon assays indicated that the polymerase activity was elevated by these substitutions. Notably, the PB2-V598T/I substitutions substantially increased virus replication and virulence in mice. Together, we demonstrated that the substitutions PB2-V598T/I contributed to higher IAV replication and virulence in mammals, which added to the knowledge of IAV virulence determinants and benefited the surveillance of IAVs.

關鍵詞：influenza A virus; PB2; PB2-K389R; PB2-V598T/I; virulence

來源出版物：Virology, 2017, 501: 92-101

聯(lián)系郵箱：Chu, H; hinchu@hku.hk

Rapid and sensitive detection of RNA viruses based on reverse transcription loop-mediated isothermal amplification, magnetic nanoparticles, and chemiluminescence

Wang, JH; Lu, P; Yan, JN; et al.

Abstract: RNA viruses, particularly, the highly pathogenic avian influenza (HPAI) virus, pose serious health concerns, and cause huge economic losses worldwide. Diagnostic tools for the early detection of these deadly RNA viruses are urgently needed to implement treatment and disease control strategies. Conventional reverse transcription polymerase chain reaction (RT-PCR)-based chemiluminescent (RT-PCR-CL) detection is frequently used for the diagnosis of viral infections. However, the requirements for expensive PCR machines and longer thermocycling times are significant drawbacks. In thisstudy, we propose a method based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with chemiluminescence (CL) to detect H7N9 virus. The proposed method does not require any expensive instruments, and processing time is remarkably shortened compared to that of RT-PCR-CL. Since several factors including RT-LAMP temperature, probe concentration, hybridization temperature, and hybridization duration might affect the CL signal, each of these parameters was investigated and optimized. One thousand copies/mL of H7N9 RNA were detectable using the optimized RT- LAMP-CL method. The detection time was significantly reduced by using RT-LAMP, in comparison with conventional RT-PCR-CL. This technique holds great promise for viral detection and diagnosis, especially with regard to avian influenza virus.

來源出版物：Journal of Biomedical Nanotechnology, 2016, 12(4): 710-716

聯(lián)系郵箱：Li, ZY; sslb_112@hotmail.com

Species difference in ANP32A underlies influenza A virus polymerase host restriction

Long, JS; Giotis, ES; Moncorge, O; et al.

Abstract: Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal lowcomplexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2 (E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals.

來源出版物：Nature, 2016, 529(7584): 101-104

聯(lián)系郵箱：Barclay, WS; w.barclay@imperial.ac.uk

Both neutralizing and non-neutralizing human H7N9 influenza vaccine-induced monoclonal antibodies confer protection

Dunand, CJH; Leon, PE; Huang, M; et al.

Abstract: Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.

來源出版物：Cell Host & Microbe, 2016, 19(6): 800-813

聯(lián)系郵箱：Wilson, PC; florian.krammer@mssm.edu

PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

Xiao, CC; Ma, WJ; Sun, N; et al.

Abstract: Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles inmammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts.

來源出版物：Scientific Reports, 2016, 6, 19474

聯(lián)系郵箱：Qi, WB; qiwenbao@scau.edu.cn

Broadly-reactive neutralizing and non-neutralizing antibodies directed against the H7 influenza virus hemagglutinin reveal divergent mechanisms of protection

Tan, GS; Leon, PE; Albrecht, RA; et al.

Abstract: In the early spring of 2013, Chinese health authorities reported several cases of H7N9 influenza virus infections in humans. Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually. In order to characterize the antibody response to the H7N9 virus we generated several mouse monoclonal antibodies against the hemagglutinin of the A/Shanghai/1/13 (H7N9) virus. Of particular note are two monoclonal antibodies, 1B2 and 1H5, that show broad reactivity to divergent H7 hemagglutinins. Monoclonal antibody 1B2 binds to viruses of the Eurasian and North American H7 lineages and monoclonal antibody 1H5 reacts broadly to virus isolates of the Eurasian lineage. Interestingly, 1B2 shows broad hemagglutination inhibiting and neutralizing activity, while 1H5 fails to inhibit hemagglutination and demonstrates no neutralizing activity in vitro. However, both monoclonal antibodies were highly protective in an in

vivo passive transfer challenge model in mice, even at low doses. Experiments using mutant antibodies that lack the ability for Fc/Fc-receptor and Fc/complement interactions suggest that the protection provided by mAb 1H5 is, at least in part, mediated by the Fc-fragment of the mAb. These findings highlight that a protective response to a pathogen may not only be due to neutralizing antibodies, but can also be the result of highly efficacious non-neutralizing antibodies not readily detected by classical in vitro neutralization or hemagglutination inhibition assays. This is of interest because H7 influenza virus vaccines induce only low hemagglutination inhibiting antibody titers while eliciting robust antibody titers as measured by ELISA. Our data suggest that these binding but non-neutralizing antibodies contribute to protection in vivo.

來源出版物：PLoS Pathog, 2016, 12(4): e1005578

聯(lián)系郵箱：Krammer, F; Gene.Tan@mssm.edu

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

Pu, J; Wang, SG; Yin, YB; et al.

Abstract: The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant's internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010-2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.

來源出版物：Proceedings of the National Academy of Sciences, 2015, 112(2): 548-553

聯(lián)系郵箱：Liu, JH, S; ljh@cau.edu.cn

Dissemination, divergence and establishment of H7N9 influenza viruses in China

Lam, TTY; Zhou, BP; Wang, J; et al.

Abstract: Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013. It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to publichealth. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.

來源出版物：Nature, 2015, 522(7554): 102-105

聯(lián)系郵箱：Guan, Y; yguan@hku.hk

Assessment of the internal genes of influenza A (H7N9) virus contributing to high pathogenicity in mice

Bi, YH; Xie, Q; Zhang, S; et al.

Abstract: The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans. IMPORTANCE: To date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been systematically studied. Here, the H9N2 virus was used as a genetic backbone to evaluate the virulence genes of H7N9 virus in vitro and in vivo. Our data indicate that the PB2, M, and NP genes play important roles in viral infection in mice and, together with HA and NA, contribute to the high infectivity of the H7N9 virus in humans.

來源出版物：Journal of Virology, 2015, 89(1): 2-13

聯(lián)系郵箱：Gao, GF; Gaof@im.ac.cn

Differences in the epidemiology of human cases of avian influenza A (H7N9) and A (H5N1) viruses infection

Qin, Y; Horby, PW; Tsang, TK; et al.

Abstract: Background: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. Methods: We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). Results: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = 0.007; median age 59 years vs 31, P ＜ 0.001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for Rwas 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). Conclusions: The results are consistent withan ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.

來源出版物：Clinical Infectious Diseases, 2015, 61(4): 563-571

聯(lián)系郵箱：Yu, HJ; yuhj@chinacdc.cn

Characterization of drug-resistant influenza A (H7N9) variants isolated from an oseltamivir-treated patient in Taiwan

Marjuki, H; Mishin, VP; Chesnokov, AP; et al.

Abstract: Background: Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited. Methods: Four NA variants of A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NAI222K, NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice, and ferrets. Results: NA-R292K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA -R292K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA-I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NAR292K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract but produced only mild illness. NA-R292K virus, showed reduced replicative fitness in this animal model. Conclusions: Our data highlight challenges in assessment of the replicative fitness of H7N9 NA variants that emerged in NAI-treated patients.

關鍵詞：influenza virus; H7N9; oseltamivir; peramivir; R292K; E119V; I222K; I222R; mice; ferrets

來源出版物：Journal of Infectious Diseases, 2015, 211(2): 249-257

聯(lián)系郵箱：Gubareva, LV; lgubareva@cdc.gov

編輯：王微

Quantitative risk analysis of the novel H7N9 virus in environments associated with H9 avian influenza virus, Zhejiang province, China

He, F; Lin, JF; Wang, XY; et al.

H9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 449, 95% confidence interval 379-531). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 493 (rural vs. urban area), 4680 (live poultry markets vs. other premises), 686 (Huzhou vs. Hangzhou prefecture), 4067 (year 2015 vs. 2013), and 963 (sewage from cleaning poultry vs. poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment.