Avian Influenza A(H5N1) Virus in Egypt.

PubMed

Kayali, Ghazi; Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S; Maatouq, Asmaa M; Cai, Zhipeng; McKenzie, Pamela P; Webby, Richard J; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A

2016-03-01

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

Avian Influenza A(H5N1) Virus in Egypt

PubMed Central

Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S.; Maatouq, Asmaa M.; Cai, Zhipeng; McKenzie, Pamela P.; Webby, Richard J.; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A.

2016-01-01

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt. PMID:26886164

Avian influenza A (H5N1).

PubMed

de Jong, Menno D; Hien, Tran Tinh

2006-01-01

Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.

Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan province, China.

PubMed

Xu, Wen; Li, Hong; Jiang, Li

2016-01-01

Highly pathogenic avian influenza A H5N6 virus has caused four human infections in China. This study reports the preliminary findings of the first known human case of H5N6 in Yunnan province. The patient initially developed symptoms of sore throat and coughing on 27 January 2015. The disease rapidly progressed to severe pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome and the patient died on 6 February. Virological analysis determined that the virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for mammalian adaptation and amantadine resistance. Environmental investigation found H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs and sewage from local live poultry markets by real-time RT-PCR. These findings suggest that the expanding and enhancing of surveillance in both avian and humans are necessary to monitor the evolution of H5 influenza virus and to facilitate early detection of suspected cases.

Limited pathogenicity and transmissibility of Korean highly pathogenic avian influenza H5N6 clade 2.3.4.4 in ferrets.

PubMed

Noh, J-Y; Lee, D-H; Yuk, S-S; Kwon, J-H; Tseren-Ochir, E-O; Hong, W-T; Jeong, J-H; Jeong, S; Song, C-S

2018-04-19

The pathogenicity and transmissibility of a reassortant clade 2.3.4.4 avian influenza A (H5N6) virus were evaluated in ferrets. Virus excretion was detected in the upper respiratory tract, but the ferrets did not show any clinical signs of infection. Transmission did not occur between cohoused or respiratory droplet-contact ferrets. © 2018 Blackwell Verlag GmbH.

Low risk of avian influenza A (H5N6) transmission to depopulation workers in Korea.

PubMed

Ryu, Sukhyun; Lim, Jun-Sik; Cowling, Benjamin J; Chun, Byung Chul

2018-05-01

An outbreak of highly pathogenic avian influenza A (H5N6) virus occurred between November 20, 2016, and March 1, 2017 in poultry farms, in the Gyeonggi Province, Republic of Korea. To identify the risk of transmission of H5N6 to depopulation workers, active and passive surveillance was conducted. Virological testing of respiratory swabs with real-time reverse transcription-polymerase chain reaction was performed for workers who reported respiratory symptoms. Among 4633 depopulation workers, 22 reported respiratory symptoms, but all tested negative for H5N6. Personal protective equipment in addition to antiviral prophylaxis was adequate to limit transmission of H5N6 from poultry to humans. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses

PubMed Central

Zhou, Hong; Cox, Nancy J.; Donis, Ruben O.

2008-01-01

The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian–human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency in vitro, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs. PMID:18497857

Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China.

PubMed

Bi, Yuhai; Chen, Quanjiao; Wang, Qianli; Chen, Jianjun; Jin, Tao; Wong, Gary; Quan, Chuansong; Liu, Jun; Wu, Jun; Yin, Renfu; Zhao, Lihua; Li, Mingxin; Ding, Zhuang; Zou, Rongrong; Xu, Wen; Li, Hong; Wang, Huijun; Tian, Kegong; Fu, Guanghua; Huang, Yu; Shestopalov, Alexander; Li, Shoujun; Xu, Bing; Yu, Hongjie; Luo, Tingrong; Lu, Lin; Xu, Xun; Luo, Yang; Liu, Yingxia; Shi, Weifeng; Liu, Di; Gao, George Fu

2016-12-14

Constant surveillance of live poultry markets (LPMs) is currently the best way to predict and identify emerging avian influenza viruses (AIVs) that pose a potential threat to public health. Through surveillance of LPMs from 16 provinces and municipalities in China during 2014-2016, we identified 3,174 AIV-positive samples and isolated and sequenced 1,135 AIVs covering 31 subtypes. Our analysis shows that H5N6 has replaced H5N1 as one of the dominant AIV subtypes in southern China, especially in ducks. Phylogenetic analysis reveals that H5N6 arose from reassortments of H5 and H6N6 viruses, with the hemagglutinin and neuraminidase combinations being strongly lineage specific. H5N6 viruses constitute at least 34 distinct genotypes derived from various evolutionary pathways. Notably, genotype G1.2 virus, with internal genes from the chicken H9N2/H7N9 gene pool, was responsible for at least five human H5N6 infections. Our findings highlight H5N6 AIVs as potential threats to public health and agriculture. Copyright © 2016. Published by Elsevier Inc.

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

PubMed Central

Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James R.; Cheng, Xing; Treanor, John J.; Jin, Hong

2015-01-01

ABSTRACT H3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. A live attenuated, cold-adapted (ca) H3N8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin (HA) and neuraminidase (NA) genes from the A/blue-winged teal/Texas/Sg-00079/2007 (H3N8) (tl/TX/079/07) wt virus and the six internal protein gene segments from the ca influenza A virus vaccine donor strain, A/Ann Arbor/6/60 ca (H2N2), the backbone of the licensed seasonal live attenuated influenza vaccine. One dose of the tl/TX/079/07 ca vaccine induced a robust neutralizing antibody response against the homologous (tl/TX/079/07) and two heterologous influenza viruses, including the recently emerged A/harbor seal/New Hampshire/179629/2011 (H3N8) and A/northern pintail/Alaska/44228-129/2006 (H3N8) viruses, and conferred robust protection against the homologous and heterologous influenza viruses. We also analyzed human sera against the tl/TX/079/07 H3N8 avian influenza virus and observed low but detectable antibody reactivity in elderly subjects, suggesting that older H3N2 influenza viruses confer some cross-reactive antibody. The latter observation was confirmed in a ferret study. The safety, immunogenicity, and efficacy of the tl/TX/079/07 ca vaccine in mice and ferrets support further evaluation of this vaccine in humans for use in the event of transmission of an H3N8 avian influenza virus to humans. The human and ferret serology data suggest that a single dose of the vaccine may be sufficient in older subjects. IMPORTANCE Although natural infection of humans with an avian H3N8 influenza virus has not yet been reported, this influenza virus subtype has already crossed the species barrier and productively infected mammals. Pandemic preparedness is an

Avian Influenza A (H7N9) Virus

MedlinePlus

... Variant Pandemic Other Asian Lineage Avian Influenza A (H7N9) Virus Language: English (US) Español Recommend on Facebook ... Guidance Laboratorian Guidance H7N9 Images Additional Information Asian H7N9 Outbreak Characterization Asian H7N9 virus infections in poultry ...

Protection of poultry against the 2012 Mexican H7N3 highly pathogenic avian influenza virus with inactivated H7 avian influenza vaccines

USDA-ARS?s Scientific Manuscript database

In June of 2012, an outbreak of highly pathogenic avian influenza (HPAI) H7N3 was reported poultry in Jalisco, Mexico. Since that time the virus has spread to the surrounding States of Guanajuato and Aguascalientes and new outbreaks continue to be reported. To date more than 25 million birds have di...

Serological evidence for avian H9N2 influenza virus infections among Romanian agriculture workers.

PubMed

Coman, Alexandru; Maftei, Daniel N; Krueger, Whitney S; Heil, Gary L; Friary, John A; Chereches, Razvan M; Sirlincan, Emanuela; Bria, Paul; Dragnea, Claudiu; Kasler, Iosif; Gray, Gregory C

2013-12-01

In recent years, wild birds have introduced multiple highly pathogenic avian influenza (HPAI) H5N1 virus infections in Romanian poultry. In 2005 HPAI infections were widespread among domestic poultry and anecdotal reports suggested domestic pigs may also have been exposed. We sought to examine evidence for zoonotic influenza infections among Romanian agriculture workers. Between 2009 and 2010, 363 adult participants were enrolled in a cross-sectional, seroepidemiological study. Confined animal feeding operation (CAFO) swine workers in Tulcea and small, traditional backyard farmers in Cluj-Napoca were enrolled, as well as a non-animal exposed control group from Cluj-Napoca. Enrollment sera were examined for serological evidence of previous infection with 9 avian and 3 human influenza virus strains. Serologic assays showed no evidence of previous infection with 7 low pathogenic avian influenza viruses or with HPAI H5N1. However, 33 participants (9.1%) had elevated microneutralization antibody titers against avian-like A/Hong Kong/1073/1999(H9N2), 5 with titers ≥ 1:80 whom all reported exposure to poultry. Moderate poultry exposure was significantly associated with elevated titers after controlling for the subjects' age (adjusted OR = 3.6; 95% CI, 1.1-12.1). There was no evidence that previous infection with human H3N2 or H2N2 viruses were confounding the H9N2 seroreactivity. These data suggest that H9N2 virus may have circulated in Romanian poultry and occasionally infected man. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Avian influenza virus (H5N1): a threat to human health.

PubMed

Peiris, J S Malik; de Jong, Menno D; Guan, Yi

2007-04-01

Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses.

PubMed

Chen, Sujuan; Zhu, Yinbiao; Yang, Da; Yang, Yang; Shi, Shaohua; Qin, Tao; Peng, Daxin; Liu, Xiufan

2017-01-01

H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

Characterization of an H9N2 avian influenza virus from a Fringilla montifringilla brambling in northern China.

PubMed

Yuan, Jing; Xu, Lili; Bao, Linlin; Yao, Yanfeng; Deng, Wei; Li, Fengdi; Lv, Qi; Gu, Songzhi; Wei, Qiang; Qin, Chuan

2015-02-01

Avian H9N2 influenza viruses circulating in domestic poultry populations are occasionally transmitted to humans. We report the genomic characterization of an H9N2 avian influenza virus (A/Brambling/Beijing/16/2012) first isolated from a healthy Fringilla montifringilla brambling in northern China in 2012. Phylogenetic analyses revealed that this H9N2 virus belongs to the BJ/94-like sublineage. This virus had a low pathogenicity for chickens and was able to replicate at a low level in mouse lung tissue. Transmission studies in ferrets showed that this H9N2 strain shed high levels of the virus in nasal and throat swabs. In vitro receptor binding assays, the virus bound only to α-2,6 linkage receptors and not to the avian-type α-2,3 linkage receptors, suggesting that H9N2 influenza viruses present potential public health risks. Therefore, attention should be paid to H9N2 influenza viruses and the close surveillance of H9N2 viruses in poultry. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016

PubMed Central

Si, Young-Jae; Lee, In Won; Kim, Eun-Ha; Kim, Young-Il; Kwon, Hyeok-Il; Park, Su-Jin; Nguyen, Hiep Dinh; Kim, Se Mi; Kwon, Jin-Jung; Choi, Won-Suk; Beak, Yun Hee; Song, Min-Suk; Kim, Chul-Joong; Webby, Richard J.; Choi, Young-Ki

2017-01-01

A novel genotype of H5N6 influenza viruses was isolated from migratory birds in South Korea during November 2016. Domestic outbreaks of this virus were associated with die-offs of wild birds near reported poultry cases in Chungbuk province, central South Korea. Genetic analysis and animal studies demonstrated that the Korean H5N6 viruses are highly pathogenic avian influenza (HPAI) viruses and that these viruses are novel reassortants of at least three different subtypes (H5N6, H4N2 and H1N1). PMID:28079520

Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015

PubMed Central

Zhou, Jie; Wu, Jie; Zeng, Xianqiao; Huang, Guofeng; Zou, Lirong; Song, Yingchao; Gopinath, Divya; Zhang, Xin; Kang, Min; Lin, Jinyan; Cowling, Benjamin J; Lindsley, William G.; Ke, Changwen; Peiris, Joseph Sriyal Malik; Yen, Hui-Ling

2016-01-01

Zoonotic infections by avian influenza viruses occur at the human–poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls. PMID:27608369

Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015.

PubMed

Zhou, Jie; Wu, Jie; Zeng, Xianqiao; Huang, Guofeng; Zou, Lirong; Song, Yingchao; Gopinath, Divya; Zhang, Xin; Kang, Min; Lin, Jinyan; Cowling, Benjamin J; Lindsley, William G; Ke, Changwen; Peiris, Joseph Sriyal Malik; Yen, Hui-Ling

2016-09-01

Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls. This article is copyright of The Authors, 2016.

Comparative analysis of virulence of a novel, avian-origin H3N2 canine influenza virus in various host species.

PubMed

Lyoo, Kwang-Soo; Kim, Jeong-Ki; Kang, Bokyu; Moon, Hyoungjoon; Kim, Jongman; Song, Manki; Park, Bongkyun; Kim, Sang-Hyun; Webster, Robert G; Song, Daesub

2015-01-02

A novel avian-origin H3N2 canine influenza A virus (CIV) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in South Korea. We previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. In the present study, the host tropism of H3N2 CIV was examined by experimental inoculation into several host species, including chickens, pigs, mice, guinea pigs, and ferrets. The CIV infection resulted in no overt symptoms of disease in these host species. However, sero-conversion, virus shedding, and gross and histopathologic lung lesions were observed in guinea pig and ferrets but not in pigs, or mice. Based on the genetic similarity of our H3N2 CIV with currently circulating avian influenza viruses and the presence of α-2,3-linked rather than α-2,6-linked sialic acid receptors in the respiratory tract of dogs, we believed that this strain of CIV would have avian virus-like receptor specificity, but that seems to be contrary to our findings in the present study. Further studies are needed to determine the co-receptors of hemagglutinin or post-attachment factors related to virus internalization or pathogenesis in other animals. Copyright © 2014 Elsevier B.V. All rights reserved.

Reassortment process after co-infection of pigs with avian H1N1 and swine H3N2 influenza viruses.

PubMed

Urbaniak, Kinga; Markowska-Daniel, Iwona; Kowalczyk, Andrzej; Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Frącek, Barbara; Pejsak, Zygmunt

2017-07-08

The influenza A virus is highly variable, which, to some degree, is caused by the reassortment of viral genetic material. This process plays a major role in the generation of novel influenza virus strains that can emerge in a new host population. Due to the susceptibility of pigs to infections with avian, swine and human influenza viruses, they are considered intermediate hosts for the adaptation of the avian influenza virus to humans. In order to test the reassortment process in pigs, they were co-infected with H3N2 A/swine/Gent/172/2008 (Gent/08) and H1N1 A/duck/Italy/1447/2005 (Italy/05) and co-housed with a group of naïve piglets. The Gent/08 strains dominated over Italy/05, but reassortment occurred. The reassortant strains of the H1N1 subtype (12.5%) with one gene (NP or M) of swine-origin were identified in the nasal discharge of the contact-exposed piglets. These results demonstrate that despite their low efficiency, genotypically and phenotypically different influenza A viruses can undergo genetic exchange during co-infection of pigs.

Novel Reassortant Clade 2.3.4.4 Avian Influenza A(H5N8) Virus in Wild Aquatic Birds, Russia, 2016.

PubMed

Lee, Dong-Hun; Sharshov, Kirill; Swayne, David E; Kurskaya, Olga; Sobolev, Ivan; Kabilov, Marsel; Alekseev, Alexander; Irza, Victor; Shestopalov, Alexander

2017-02-01

The emergence of novel avian influenza viruses in migratory birds is of concern because of the potential for virus dissemination during fall migration. We report the identification of novel highly pathogenic avian influenza viruses of subtype H5N8, clade 2.3.4.4, and their reassortment with other avian influenza viruses in waterfowl and shorebirds of Siberia.

Preferential recognition of avian-like receptors in human influenza A H7N9 viruses.

PubMed

Xu, Rui; de Vries, Robert P; Zhu, Xueyong; Nycholat, Corwin M; McBride, Ryan; Yu, Wenli; Paulson, James C; Wilson, Ian A

2013-12-06

The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike α2-6-linked receptors and strong preference for a subset of avian-like α2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.

Current situation of H9N2 subtype avian influenza in China.

PubMed

Gu, Min; Xu, Lijun; Wang, Xiaoquan; Liu, Xiufan

2017-09-15

In China, H9N2 subtype avian influenza outbreak is firstly reported in Guangdong province in 1992. Subsequently, the disease spreads into vast majority regions nationwide and has currently become endemic there. Over vicennial genetic evolution, the viral pathogenicity and transmissibility have showed an increasing trend as year goes by, posing serious threat to poultry industry. In addition, H9N2 has demonstrated significance to public health as it could not only directly infect mankind, but also donate partial or even whole cassette of internal genes to generate novel human-lethal reassortants like H5N1, H7N9, H10N8 and H5N6 viruses. In this review, we mainly focused on the epidemiological dynamics, biological characteristics, molecular phylogeny and vaccine strategy of H9N2 subtype avian influenza virus in China to present an overview of the situation of H9N2 in China.

Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012.

PubMed

Lopez-Martinez, Irma; Balish, Amanda; Barrera-Badillo, Gisela; Jones, Joyce; Nuñez-García, Tatiana E; Jang, Yunho; Aparicio-Antonio, Rodrigo; Azziz-Baumgartner, Eduardo; Belser, Jessica A; Ramirez-Gonzalez, José E; Pedersen, Janice C; Ortiz-Alcantara, Joanna; Gonzalez-Duran, Elizabeth; Shu, Bo; Emery, Shannon L; Poh, Mee K; Reyes-Teran, Gustavo; Vazquez-Perez, Joel A; Avila-Rios, Santiago; Uyeki, Timothy; Lindstrom, Stephen; Villanueva, Julie; Tokars, Jerome; Ruiz-Matus, Cuitláhuac; Gonzalez-Roldan, Jesus F; Schmitt, Beverly; Klimov, Alexander; Cox, Nancy; Kuri-Morales, Pablo; Davis, C Todd; Diaz-Quiñonez, José Alberto

2013-01-01

We identified 2 poultry workers with conjunctivitis caused by highly pathogenic avian influenza A(H7N3) viruses in Jalisco, Mexico. Genomic and antigenic analyses of 1 isolate indicated relatedness to poultry and wild bird subtype H7N3 viruses from North America. This isolate had a multibasic cleavage site that might have been derived from recombination with host rRNA.

The Potential of Avian H1N1 Influenza A Viruses to Replicate and Cause Disease in Mammalian Models

PubMed Central

Koçer, Zeynep A.; Krauss, Scott; Stallknecht, David E.; Rehg, Jerold E.; Webster, Robert G.

2012-01-01

H1N1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian H1N1 isolates of American lineage in DBA/2J mice. Thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 H1N1 viruses. Preliminary studies in BALB/cJ mice and ferrets showed that 1 of 4 isolates tested was more pathogenic than the pandemic 2009 H1N1 viruses in BALB/cJ mice, and 1 of 2 strains transmitted both by direct and respiratory-droplet contact in ferrets. Preliminary studies of other avian subtypes (H2, H3, H4, H6, H10, H12) in DBA/2J mice showed lower pathogenicity than the avian H1N1 viruses. These findings suggest that avian H1N1 influenza viruses are unique among influenza A viruses in their potential to infect mammals. PMID:22848544

Convergent Evolution of Human-Isolated H7N9 Avian Influenza A Viruses.

PubMed

Xiang, Dan; Shen, Xuejuan; Pu, Zhiqing; Irwin, David M; Liao, Ming; Shen, Yongyi

2018-05-05

Avian influenza A virus H7N9 has caused 5 epidemic waves of human infections in China since 2013. Avian influenza A viruses may face strong selection to adapt to novel conditions when establishing themselves in humans. In this study, we sought to determine whether adaptive evolution had occurred in human-isolated H7N9 viruses. We evaluated all available genomes of H7N9 avian influenza A virus. Maximum likelihood trees were separately reconstructed for all 8 genes. Signals of positive selection and convergent evolution were then detected on branches that lead to changes in host tropism (from avian to human). We found that 3 genes had significant signals of positive selection (all of them P < .05). In addition, we detected 34 sites having significant signals for parallel evolution in 8 genes (all of them P < .05), including 7 well-known sites (Q591K, E627K, and D701N in PB2 gene; R156K, V202A, and L244Q in HA; and R289K in NA) that play roles in crossing species barriers for avian influenza A viruses. Our study suggests that, during infection in humans, H7N9 viruses have undergone adaptive evolution to adapt to their new host environment and that the sites where parallel evolution occurred might play roles in crossing species barriers and respond to the new selection pressures arising from their new host environments.

Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016.

PubMed

Si, Young-Jae; Lee, In Won; Kim, Eun-Ha; Kim, Young-Il; Kwon, Hyeok-Il; Park, Su-Jin; Nguyen, Hiep Dinh; Kim, Se Mi; Kwon, Jin-Jung; Choi, Won-Suk; Beak, Yun Hee; Song, Min-Suk; Kim, Chul-Joong; Webby, Richard J; Choi, Young-Ki

2017-01-05

A novel genotype of H5N6 influenza viruses was isolated from migratory birds in South Korea during November 2016. Domestic outbreaks of this virus were associated with die-offs of wild birds near reported poultry cases in Chungbuk province, central South Korea. Genetic analysis and animal studies demonstrated that the Korean H5N6 viruses are highly pathogenic avian influenza (HPAI) viruses and that these viruses are novel reassortants of at least three different subtypes (H5N6, H4N2 and H1N1). This article is copyright of The Authors, 2017.

Avian influenza virus H9N2 infections in farmed minks.

PubMed

Zhang, Chuanmei; Xuan, Yang; Shan, Hu; Yang, Haiyan; Wang, Jianlin; Wang, Ke; Li, Guimei; Qiao, Jian

2015-11-02

The prevalence of avian H9N2 viruses throughout Asia, along with their demonstrated ability to infect mammals, puts them high on the list of influenza viruses with pandemic potential for humans. In this study, we investigated whether H9N2 viruses could infect farmed minks. First, we conducted a serological survey for avian influenza virus antibodies on a random sample of the field-trial population of farmed minks. Then we inoculated farmed minks with A/Chicken/Hebei/4/2008 H9N2 viruses and observed the potential pathogenicity of H9N2 virus and virus shedding in infected minks. H9 influenza antibodies could be detected in most farmed minks with a higher seropositivity, which indicated that farmed minks had the high prevalence of exposure to H9 viruses. After infection, the minks displayed the slight clinical signs including lethargy and initial weight loss. The infected lungs showed the mild diffuse pneumonia with thickened alveolar walls and inflammatory cellular infiltration. Influenza virus detection showed that viruses were detected in the allantoic fluids inoculated supernatant of lung tissues at 3 and 7 days post-infection (dpi), and found in the nasal swabs of H9N2-infected minks at 3-11 dpi, suggesting that H9N2 viruses replicated in the respiratory organ, were then shed outwards. HI antibody test showed that antibody levels began to rise at 7 dpi. Our data provided the serological and experimental evidences that strongly suggested farmed minks under the natural state were susceptible to H9N2 viral infection and might be the H9N2 virus carriers. It is imperative to strengthen the H9N2 viral monitoring in farmed minks and pay urgent attention to prevent and control new influenza viruses pandemic prevalence.

Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tzarum, Netanel; de Vries, Robert P.; Zhu, Xueyong

Avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (RBS) of the viral hemagglutinin (HA) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. We find that, although the H6 HA RBS contains D190V and G228S substitutions that potentially promote human receptor binding, recombinant H6 HA preferentially binds α2-3-linked sialosides, indicating no adaptation to human receptors. Crystal structures of H6 HA with avian and humanmore » receptor analogs reveal that H6 HA preferentially interacts with avian receptor analogs. Lastly, this binding mechanism differs from other HA subtypes due to a unique combination of RBS residues, highlighting additional variation in HA-receptor interactions and the challenges in predicting which influenza strains and subtypes can infect humans and cause pandemics.« less

Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus

DOE PAGES

Tzarum, Netanel; de Vries, Robert P.; Zhu, Xueyong; ...

2015-03-11

Avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (RBS) of the viral hemagglutinin (HA) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. We find that, although the H6 HA RBS contains D190V and G228S substitutions that potentially promote human receptor binding, recombinant H6 HA preferentially binds α2-3-linked sialosides, indicating no adaptation to human receptors. Crystal structures of H6 HA with avian and humanmore » receptor analogs reveal that H6 HA preferentially interacts with avian receptor analogs. Lastly, this binding mechanism differs from other HA subtypes due to a unique combination of RBS residues, highlighting additional variation in HA-receptor interactions and the challenges in predicting which influenza strains and subtypes can infect humans and cause pandemics.« less

Structure and receptor binding preferences of recombinant hemagglutinins from avian and human H6 and H10 influenza A virus subtypes.

PubMed

Yang, Hua; Carney, Paul J; Chang, Jessie C; Villanueva, Julie M; Stevens, James

2015-04-01

During 2013, three new avian influenza A virus subtypes, A(H7N9), A(H6N1), and A(H10N8), resulted in human infections. While the A(H7N9) virus resulted in a significant epidemic in China across 19 provinces and municipalities, both A(H6N1) and A(H10N8) viruses resulted in only a few human infections. This study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. The detailed structural and glycan microarray analyses presented here highlight the idea that both A(H6N1) and A(H10N8) virus hemagglutinins retain a strong avian receptor binding preference and thus currently pose a low risk for sustained human infections. Human infections with zoonotic influenza virus subtypes continue to be a great public health concern. We report detailed structural analysis and glycan microarray data for recombinant hemagglutinins from A(H6N1) and A(H10N8) viruses, isolated from human infections in 2013, and compare them with hemagglutinins of avian origin. This is the first structural report of an H6 hemagglutinin, and our results should further the understanding of these viruses and provide useful information to aid in the continuous surveillance of these zoonotic influenza viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Role for migratory wild birds in the global spread of avian influenza H5N8

USGS Publications Warehouse

,; Ip, Hon S.

2016-01-01

Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade 2.3.4.4) virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014–2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade 2.3.4.4 virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes. Improving our understanding of the circumpolar circulation of avian influenza viruses in migratory waterfowl will help to provide early warning of threats from avian influenza to poultry, and potentially human, health.

[Trends in and challenges for highly pathogenic avian influenza A (H5N1)].

PubMed

Kudo, Koichiro; Manabe, Toshie; Izumi, Shinyu; Takasaki, Jin

2010-09-01

A new pandemic influenza A (H1N1) virus had emerged and rapidly spread throughout the world. The clinical pathological observations associated with severe cases of pandemic (H1N1) 2009 are similar to that of high pathogenic avian influenza (H5N1). In order to find the most effective treatment methods for this pandemic influenza (H1N1), we describe our experiences, investigations and collaboration studies of avian influenza (H5N1) in Vietnam in association of our cooperative study of pandemic (H1N1) 2009 in Mexico. Effective treatment methods for critical illness due to influenza will be discussed from medical, regional and global points of view, which may be applied for the treatment of any type of influenza virus.

Detection of reassortant H5N6 clade 2.3.4.4 highly pathogenic avian influenza virus in a black-faced spoonbill (Platalea minor) found dead, Taiwan, 2017

USDA-ARS?s Scientific Manuscript database

H5N1 high pathogenicity avian influenza virus (HPAIV) emerged in 1996 in Guangdong China (A/goose/Guangdong/1/1996, Gs/GD) has caused outbreaks in over 80 countries throughout Eurasia, Africa, and North America. A H5N6 HPAIV clade 2.3.4.4, A/ black-faced spoonbill /Taiwan/DB645/2017 (SB/Tw/17), was ...

Contemporary Avian Influenza A Virus Subtype H1, H6, H7, H10, and H15 Hemagglutinin Genes Encode a Mammalian Virulence Factor Similar to the 1918 Pandemic Virus H1 Hemagglutinin

PubMed Central

Qi, Li; Pujanauski, Lindsey M.; Davis, A. Sally; Schwartzman, Louis M.; Chertow, Daniel S.; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L.; Slemons, Richard D.; Walters, Kathie-Anne; Kash, John C.

2014-01-01

ABSTRACT Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals. PMID:25406382

Role for migratory wild birds in the global spread of avian influenza H5N8.

PubMed

2016-10-14

Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade 2.3.4.4) virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014-2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade 2.3.4.4 virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes. Improving our understanding of the circumpolar circulation of avian influenza viruses in migratory waterfowl will help to provide early warning of threats from avian influenza to poultry, and potentially human, health. Copyright © 2016, American Association for the Advancement of Science.

Contemporary avian influenza A virus subtype H1, H6, H7, H10, and H15 hemagglutinin genes encode a mammalian virulence factor similar to the 1918 pandemic virus H1 hemagglutinin.

PubMed

Qi, Li; Pujanauski, Lindsey M; Davis, A Sally; Schwartzman, Louis M; Chertow, Daniel S; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L; Slemons, Richard D; Walters, Kathie-Anne; Kash, John C; Taubenberger, Jeffery K

2014-11-18

Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals. Influenza viruses from birds can cause outbreaks in humans and may contribute to the development of pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its main surface protein, an H1 subtype hemagglutinin, was identified as a key mammalian virulence factor. In a previous study, a 1918 virus expressing an avian H1 gene was as virulent in mice as the reconstructed 1918 virus. Here, a set of avian influenza viruses was constructed, differing only by hemagglutinin subtype. Viruses with the avian H1, H6, H7, H10, and H15 subtypes caused severe disease in mice and damaged human lung cells. Consequently, infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals, and therefore surveillance for human infections

Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark.

PubMed

Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik; Nielsen, Jens; Bøtner, Anette; Heegaard, Peter M H; Fomsgaard, Anders; Viuff, Birgitte; Hjulsager, Charlotte Kristiane

2013-09-18

The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an "avian-like" H1N1 virus by an experimental infection study. Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an "avian-like" H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European "avian-like" H1-gene and a European "swine-like" N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish "avian-like" H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. The "avian-like" H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine "avian-like" H1N1 and H3N2. The Danish

Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

PubMed Central

2013-01-01

Background The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. Methods Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. Results The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene and a European “swine-like” N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish “avian-like” H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. Conclusions The “avian-like” H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant

Influenza A (H3N2) Variant Virus

MedlinePlus

... When Planning Fairs Key Facts for People Exhibiting Pigs at Fairs News & Highlights Materials & Resources Publications & Resources ... What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus ...

Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds--United States, December 2014-January 2015.

PubMed

Jhung, Michael A; Nelson, Deborah I

2015-02-06

During December 15, 2014-January 16, 2015, the U.S. Department of Agriculture received 14 reports of birds infected with Asian-origin, highly pathogenic avian influenza A (HPAI) (H5N2), (H5N8), and (H5N1) viruses. These reports represent the first reported infections with these viruses in U.S. wild or domestic birds. Although these viruses are not known to have caused disease in humans, their appearance in North America might increase the likelihood of human infection in the United States. Human infection with other avian influenza viruses, such as HPAI (H5N1) and (H5N6) viruses and (H7N9) virus, has been associated with severe, sometimes fatal, disease, usually following contact with poultry.

Genetic analysis and biological characteristics of different internal gene origin H5N6 reassortment avian influenza virus in China in 2016.

PubMed

Sun, Wenqiang; Li, Jiaxin; Hu, Jiao; Jiang, Daxiu; Xing, Chaonan; Zhan, Tiansong; Liu, Xiufan

2018-06-01

Clade 2.3.4.4 of H5N6 subtype Avian Influenza Viruses (AIVs) has become dominant clade in South-East Asia. So far, a total of 16 cases of human infection, including 6 deaths, have been confirmed since 2014. In this study, we systematically investigated the genetic evolution and biological characteristics of these viruses. We first carried out phylogenetic and statistical analysis of all H5N6 viruses that were downloaded from Influenza Research Database, GISAID and isolates from our lab. We found that H5N6 AIVs continued to reassort with other AIVs subtypes since 2014. Among these H5N6 reassortments, four main gene types were identified: A (internal genes of H5N1-origin), B (PB2 of H6-origin, and others of H5N1-origin), C (internal genes of H9-origin) and D (PB2 of H6-origin and PB1of H3-origin, and others of H5N1). In addition, after several years of evolution, gene type D is currently the dominant gene type. To systematically compare the genetic and evolutionary characteristics and pathogenicity of these viruses, four H5N6 AIVs of different gene types were selected for further analysis. S4, XZ6, GD1602 and YZ587 virus represented gene type A, B, C and D, respectively. Their NA genes were all originated from H6 and their whole genome showed a high similarity with human isolates. All these isolates could both bind with SA-α2,3 Gal and SA-α2,6 Gal receptors. Pathogenicity test showed that these viruses were highly pathogenic in chickens, while YZ587 showed the lowest virulence. Moreover, XZ6 and S4 viruses were highly pathogenic in ducks and moderately pathogenic in mice, while GD1602 and YZ587 viruses were no-pathogenic in these animals. Interestingly, GD1602 and YZ587-like viruses were responsible for 4 and 2 human infection cases in 2016, respectively. Therefore, our study showed that the YZ587 virus which has mixed internal genes, showed lower virulence in avian species and mammals compared to other genotype viruses. Overall, our findings suggest that the H

Isolation and genetic characterization of avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China.

PubMed

Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi

2009-08-21

As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.

Short communication: isolation and phylogenetic analysis of an avian-origin H3N2 canine influenza virus in dog shelter, China.

PubMed

Su, Shuo; Yuan, Ziguo; Chen, Jidang; Xie, Jiexiong; Li, Huatao; Huang, Zhen; Zhang, Minze; Du, Guohao; Chen, Zhongming; Tu, Liqing; Zou, Yufei; Miao, Junhao; Wang, Hui; Jia, Kun; Li, Shoujun

2013-06-01

A H3N2 canine influenza virus, A/canine/Guangdong/3/2011 (H3N2), was isolated from roaming dogs in rural China. Sequence and phylogenetic analysis of eight gene segments revealed that the A/canine/Guangdong/3/2011 (H3N2) was most similar to a recent H3N2 canine influenza virus isolated in cats from South Korea, which originated from an avian strain. To our knowledge, this is the first report of an avian-origin H3N2 CIV which was isolated from roaming dogs in China. The epidemiologic information provided herein suggests that continued study is required to determine if this virus could be established in the roaming dog population in rural China and pose potential threats to public health.

Reassortant Avian Influenza A(H5N1) Viruses with H9N2-PB1 Gene in Poultry, Bangladesh

PubMed Central

Yamage, Mat; Dauphin, Gwenaëlle; Claes, Filip; Ahmed, Garba; Giasuddin, Mohammed; Salviato, Annalisa; Ormelli, Silvia; Bonfante, Francesco; Schivo, Alessia; Cattoli, Giovanni

2013-01-01

Bangladesh has reported a high number of outbreaks of highly pathogenic avian influenza (HPAI) (H5N1) in poultry. We identified a natural reassortant HPAI (H5N1) virus containing a H9N2-PB1 gene in poultry in Bangladesh. Our findings highlight the risks for prolonged co-circulation of avian influenza viruses and the need to monitor their evolution. PMID:24047513

H9N2 low pathogenic avian influenza: Should we be afraid?

USDA-ARS?s Scientific Manuscript database

The H9N2 low pathogenic avian influenza (LPAI) is probably the most widespread avian influenza subtype in poultry around the world being endemic in a large part of Asia, the Middle East, Northern Africa, and in Germany. Currently, there is no standardized clade system to describe the antigenic vari...

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011.

PubMed

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi; Mai, Le Quynh

2014-01-01

Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. The overall seroprevalence was 6.1% (95% confidence interval: 4.6-8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian-human transmission of influenza A(H5N1) in Viet Nam.

A Novel Activation Mechanism of Avian Influenza Virus H9N2 by Furin

PubMed Central

Tse, Longping V.; Hamilton, Alice M.; Friling, Tamar

2014-01-01

Avian influenza virus H9N2 is prevalent in waterfowl and has become endemic in poultry in Asia and the Middle East. H9N2 influenza viruses have served as a reservoir of internal genes for other avian influenza viruses that infect humans, and several cases of human infection by H9N2 influenza viruses have indicated its pandemic potential. Fortunately, an extensive surveillance program enables close monitoring of H9N2 influenza viruses worldwide and has generated a large repository of virus sequences and phylogenetic information. Despite the large quantity of sequences in different databases, very little is known about specific virus isolates and their pathogenesis. Here, we characterize a low-pathogenicity avian influenza virus, A/chicken/Israel/810/2001 (H9N2) (Israel810), which is representative of influenza virus strains that have caused severe morbidity and mortality in poultry farms. We show that under certain circumstances the Israel810 hemagglutinin (HA) can be activated by furin, a hallmark of highly pathogenic avian influenza virus. We demonstrate that Israel810 HA can be cleaved in cells with high levels of furin expression and that a mutation that eliminates a glycosylation site in HA1 allows the Israel810 HA to gain universal cleavage in cell culture. Pseudoparticles generated from Israel810 HA, or the glycosylation mutant, transduce cells efficiently. In contrast, introduction of a polybasic cleavage site into Israel810 HA leads to pseudoviruses that are compromised for transduction. Our data indicate a mechanism for an H9N2 evolutionary pathway that may allow it to gain virulence in a distinct manner from H5 and H7 influenza viruses. PMID:24257604

The avian-origin H3N2 canine influenza virus has limited replication in swine

USDA-ARS?s Scientific Manuscript database

A genetically and antigenically distinct H3N2 canine influenza of avian-origin was detected in March of 2015 in Chicago, Illinois. A subsequent outbreak was reported with over 1,000 dogs in the Midwest affected. The potential for canine-to-swine transmission was unknown. Experimental infection in pi...

A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

PubMed

Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

2016-02-01

Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

PubMed

Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

2015-04-01

The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2

The Avian-Origin PB1 Gene Segment Facilitated Replication and Transmissibility of the H3N2/1968 Pandemic Influenza Virus

PubMed Central

Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter

2015-01-01

ABSTRACT The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603–4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. IMPORTANCE Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the

Global alert to avian influenza virus infection: From H5N1 to H7N9

PubMed Central

Poovorawan, Yong; Pyungporn, Sunchai; Prachayangprecha, Slinporn; Makkoch, Jarika

2013-01-01

Outbreak of a novel influenza virus is usually triggered by mutational change due to the process known as ‘antigenic shift’ or re-assortment process that allows animal-to-human or avian-to-human transmission. Birds are a natural reservoir for the influenza virus, and subtypes H5, H7, and H9 have all caused outbreaks of avian influenza in human populations. An especially notorious strain is the HPAI influenza virus H5N1, which has a mortality rate of approximately 60% and which has resulted in numerous hospitalizations, deaths, and significant economic loss. In March 2013, in Eastern China, there was an outbreak of the novel H7N9 influenza virus, which although less pathogenic in avian species, resulted in 131 confirmed cases and 36 deaths in humans over a two-month span. The rapid outbreak of this virus caused global concern but resulted in international cooperation to control the outbreak. Furthermore, cooperation led to valuable research-sharing including genome sequencing of the virus, the development of rapid and specific diagnosis, specimen sharing for future studies, and vaccine development. Although a H7N9 pandemic in the human population is possible due to its rapid transmissibility and extensive surveillance, the closure of the live-bird market will help mitigate the possibility of another H7N9 outbreak. In addition, further research into the source of the outbreak, pathogenicity of the virus, and the development of specific and sensitive detection assays will be essential for controlling and preparing for future H7N9 outbreaks. PMID:23916331

Yeast Surface-Displayed H5N1 Avian Influenza Vaccines

PubMed Central

Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey

2016-01-01

Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309

Surveillance for Asian H5N1 avian influenza in the United States

USGS Publications Warehouse

Ip, Hon S.; Slota, Paul G.

2006-01-01

Increasing concern over the potential for migratory birds to introduce the Asian H5N1 strain of avian influenza to North America prompted the White House Policy Coordinating Committee for Pandemic Influenza Preparedness to request that the U.S. Departments of Agriculture (USDA) and Interior (DOI) develop a plan for the early detection of highly pathogenic avian influenza (HPAI) in the United States. To promote coordination among wildlife, agriculture, and human health agencies on HPAI surveillance efforts, the two Departments worked with representatives from the U.S. Department of Health and Human Services, the International Association of Fish and Wildlife Agencies, and the Alaska Department of Fish and Game to develop the U.S. Interagency Strategic Plan for Early Detection of Asian H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds.

Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses.

PubMed

Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

2016-02-24

The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses.

Transmissibility of novel H7N9 and H9N2 avian influenza viruses between chickens and ferrets.

PubMed

Ku, Keun Bon; Park, Eun Hye; Yum, Jung; Kim, Heui Man; Kang, Young Myong; Kim, Jeong Cheol; Kim, Ji An; Kim, Hyun Soo; Seo, Sang Heui

2014-02-01

Previous studies have shown that the H7N9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. Here, we studied the infectivity of the H7N9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. The H7N9 virus (A/Anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. H7N9 virus was shed from chicken tracheae for only 2 days after infection and from chicken cloacae for only 1 day after infection, while the H9N2 avian influenza virus, which is endemic in chickens in many Asian countries, was shed from tracheae and cloacae for 8 days after infection. Taken together, our results suggest that chickens may be a poor agent of transmission for the H7N9 virus to other chickens and to mammals, including humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Transcriptomic characterization of the novel avian-origin influenza A (H7N9) virus: specific host response and responses intermediate between avian (H5N1 and H7N7) and human (H3N2) viruses and implications for treatment options.

PubMed

Josset, Laurence; Zeng, Hui; Kelly, Sara M; Tumpey, Terrence M; Katze, Michael G

2014-02-04

A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in 2013, causing mild to lethal human respiratory infections. H7N9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host response closer to that with human or avian IAV is important in order to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV. The transcriptomic response to H7N9 was highly specific to this strain but was more similar to the response to human H3N2 than to that to other avian IAVs. H7N9 and H3N2 both elicited responses related to eicosanoid signaling and chromatin modification, whereas H7N9 specifically induced genes regulating the cell cycle and transcription. Among avian IAVs, the response to H7N9 was closest to that elicited by H5N1 virus. Host responses common to H7N9 and the other avian viruses included the lack of induction of the antigen presentation pathway and reduced proinflammatory cytokine induction compared to that with H3N2. Repression of these responses could have an important impact on the immunogenicity and virulence of H7N9 in humans. Finally, using a genome-based drug repurposing approach, we identified several drugs predicted to regulate the host response to H7N9 that may act as potential antivirals, including several kinase inhibitors, as well as FDA-approved drugs, such as troglitazone and minocycline. Importantly, we validated that minocycline inhibited H7N9 replication in vitro, suggesting that our computational approach holds promise for identifying novel antivirals. Whether H7N9 will be the next pandemic influenza virus or will persist and sporadically infect humans from its avian reservoir, similar to H5N1, is not known yet. High-throughput profiling of the host response to infection allows rapid

The pandemic potential of avian influenza A(H7N9) virus: a review.

PubMed

Tanner, W D; Toth, D J A; Gundlapalli, A V

2015-12-01

In March 2013 the first cases of human avian influenza A(H7N9) were reported to the World Health Organization. Since that time, over 650 cases have been reported. Infections are associated with considerable morbidity and mortality, particularly within certain demographic groups. This rapid increase in cases over a brief time period is alarming and has raised concerns about the pandemic potential of the H7N9 virus. Three major factors influence the pandemic potential of an influenza virus: (1) its ability to cause human disease, (2) the immunity of the population to the virus, and (3) the transmission potential of the virus. This paper reviews what is currently known about each of these factors with respect to avian influenza A(H7N9). Currently, sustained human-to-human transmission of H7N9 has not been reported; however, population immunity to the virus is considered very low, and the virus has significant ability to cause human disease. Several statistical and geographical modelling studies have estimated and predicted the spread of the H7N9 virus in humans and avian species, and some have identified potential risk factors associated with disease transmission. Additionally, assessment tools have been developed to evaluate the pandemic potential of H7N9 and other influenza viruses. These tools could also hypothetically be used to monitor changes in the pandemic potential of a particular virus over time.

Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

USDA-ARS?s Scientific Manuscript database

Novel subtypes of Eurasian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4 such as H5N2, H5N5, H5N6, and H5N8 have been identified in China since 2008 and subsequently evolved into four genetically distinct groups (A – D) of clade 2.3.4.4...

Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

PubMed Central

Lee, Dong-Hun; Bertran, Kateri; Kwon, Jung-Hoon

2017-01-01

Novel subtypes of Asian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4, such as H5N2, H5N5, H5N6, and H5N8, have been identified in China since 2008 and have since evolved into four genetically distinct clade 2.3.4.4 groups (A–D). Since 2014, HPAI clade 2.3.4.4 viruses have spread rapidly via migratory wild aquatic birds and have evolved through reassortment with prevailing local low pathogenicity avian influenza viruses. Group A H5N8 viruses and its reassortant viruses caused outbreaks in wide geographic regions (Asia, Europe, and North America) during 2014–2015. Novel reassortant Group B H5N8 viruses caused outbreaks in Asia, Europe, and Africa during 2016–2017. Novel reassortant Group C H5N6 viruses caused outbreaks in Korea and Japan during the 2016–2017 winter season. Group D H5N6 viruses caused outbreaks in China and Vietnam. A wide range of avian species, including wild and domestic waterfowl, domestic poultry, and even zoo birds, seem to be permissive for infection by and/or transmission of clade 2.3.4.4 HPAI viruses. Further, compared to previous H5N1 HPAI viruses, these reassortant viruses show altered pathogenicity in birds. In this review, we discuss the evolution, global spread, and pathogenicity of H5 clade 2.3.4.4 HPAI viruses. PMID:28859267

Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia.

PubMed

Blair, Patrick J; Putnam, Shannon D; Krueger, Whitney S; Chum, Channimol; Wierzba, Thomas F; Heil, Gary L; Yasuda, Chadwick Y; Williams, Maya; Kasper, Matthew R; Friary, John A; Capuano, Ana W; Saphonn, Vonthanak; Peiris, Malik; Shao, Hongxia; Perez, Daniel R; Gray, Gregory C

2013-04-01

Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI) virus transmission where highly pathogenic avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

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

PubMed Central

Xiao, Chencheng; Ma, Wenjun; Sun, Na; Huang, Lihong; Li, Yaling; Zeng, Zhaoyong; Wen, Yijun; Zhang, Zaoyue; Li, Huanan; Li, Qian; Yu, Yuandi; Zheng, Yi; Liu, Shukai; Hu, Pingsheng; Zhang, Xu; Ning, Zhangyong; Qi, Wenbao; Liao, Ming

2016-01-01

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 in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V 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. PMID:26782141

Novel Reassortant H3N2 Avian Influenza Virus Isolated from Domestic Ducks in Eastern China in 2016

PubMed Central

Sun, Wenqiang; Li, Jiaxin; Hu, Jiao; Jiang, Daxiu; Ge, Zhichuang; Xing, Chaonan; Wang, Xiaoquan; Gu, Min; Liu, Xiaowen; Hu, Shunlin

2017-01-01

ABSTRACT H3 subtype avian influenza virus (AIV) poses a great threat to public health, and so investigating its epidemiology is of great importance. A novel reassortant H3N2 AIV strain was isolated from a live poultry market in eastern China. The strain’s genes originated from H1N1, H3, and H7 AIVs. Thus, the genome information of the H3N2 isolate will help to investigate further the epidemiology of H3 subtype AIVs in China. PMID:29192070

Rapid Emergence of Highly Pathogenic Avian Influenza Subtypes from a Subtype H5N1 Hemagglutinin Variant.

PubMed

de Vries, Erik; Guo, Hongbo; Dai, Meiling; Rottier, Peter J M; van Kuppeveld, Frank J M; de Haan, Cornelis A M

2015-05-01

In 2014, novel highly pathogenic avian influenza A H5N2, H5N5, H5N6, and H5N8 viruses caused outbreaks in Asia, Europe, and North America. The H5 genes of these viruses form a monophyletic group that evolved from a clade 2.3.4 H5N1 variant. This rapid emergence of new H5Nx combinations is unprecedented in the H5N1 evolutionary history.

Chicken faeces garden fertilizer: possible source of human avian influenza H5N1 infection.

PubMed

Kandun, I N; Samaan, G; Harun, S; Purba, W H; Sariwati, E; Septiawati, C; Silitonga, M; Dharmayanti, N P I; Kelly, P M; Wandra, T

2010-06-01

Avian influenza H5N1 infection in humans is typically associated with close contact with infected poultry or other infected avian species. We report on human cases of H5N1 infection in Indonesia where exposure to H5N1-infected animals could not be established, but where the investigation found chicken faeces contaminated with viable H5N1 virus in the garden fertilizer. Human cases of avian influenza H5N1 warrant extensive investigations to determine likely sources of illness and to minimize risk to others. Authorities should regulate the sale and transportation of chicken faeces as fertilizer from areas where H5N1 outbreaks are reported.

Isolation and genetic characterization of novel reassortant H6N6 subtype avian influenza viruses isolated from chickens in eastern China.

PubMed

Wu, Haibo; Lu, Rufeng; Peng, Xiuming; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

2016-07-01

H6 subtype avian influenza viruses (AIVs) possess the ability to cross the species barrier to infect mammals and pose a threat to human health. From June 2014 to July 2015, 12 H6N6 AIVs were isolated from chickens in live-poultry markets in Zhejiang Province, Eastern China. Phylogenetic analysis showed that these isolates received their genes from H6 and H9N2 subtype AIVs of poultry in China. These novel reassortant viruses showed moderate pathogenicity in mice and were able to replicate in mice without prior adaptation. Considering that novel reassorted H6N6 viruses were isolated from chickens in this study, it is possible that these chickens play an important role in the generation of novel reassorted H6N6 AIVs, and these results emphasize the need for continued surveillance of the H6N6 AIVs circulating in poultry.

Highly pathogenic avian H5N8 influenza viruses: should we be concerned?

PubMed

Tate, M D

2018-01-01

Avian influenza A viruses pose a constant threat to global human health as sporadic infections continue to occur with associated high mortality rates. To date, a number of avian influenza virus subtypes have infected humans, including H5N1, H7N9, H9N2 and H7N7. The majority of 'bird flu' cases are thought to have arisen from direct contact with infected poultry, particularly in live markets in Asia. 1 While human cases of the H5N8 subtype have not been documented as yet, there is the potential that H5N8 viruses could acquire mutations which favour infection of human cells. There is also the possibility that novel viruses with a tropism for human cells could be generated if H5N8 should reassasort with other circulating avian viruses, such as those of the H5N1 subtype. The emergence of a novel H5N8 virus with the capability of infecting humans could have drastic consequences to global health.

Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses

PubMed Central

Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

2016-01-01

The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses. PMID:26907865

Highly Pathogenic H5N1 Avian Influenza Viruses Exhibit Few Barriers to Gene Flow in Vietnam

PubMed Central

Carrel, Margaret; Wan, Xiu-Feng; Nguyen, Tung; Emch, Michael

2013-01-01

Locating areas where genetic change is inhibited can illuminate underlying processes that drive evolution of pathogens. The persistence of highly pathogenic H5N1 avian influenza in Vietnam since 2003, and the continuous molecular evolution of Vietnamese avian influenza viruses, indicates that local environmental factors are supportive not only of incidence but also of viral adaptation. This article explores whether gene flow is constant across Vietnam, or whether there exist boundary areas where gene flow exhibits discontinuity. Using a dataset of 125 highly pathogenic H5N1 avian influenza viruses, principal components analysis and wombling analysis are used to indicate the location, magnitude, and statistical significance of genetic boundaries. Results show that a small number of geographically minor boundaries to gene flow in highly pathogenic H5N1 avian influenza viruses exist in Vietnam, but that overall there is little division in genetic exchange. This suggests that differences in genetic characteristics of viruses from one region to another are not the result of barriers to H5N1 viral exchange in Vietnam, and that H5N1 avian influenza is able to spread relatively unimpeded across the country. PMID:22350419

Novel Reassortant H3N2 Avian Influenza Virus Isolated from Domestic Ducks in Eastern China in 2016.

PubMed

Sun, Wenqiang; Li, Jiaxin; Hu, Jiao; Jiang, Daxiu; Ge, Zhichuang; Xing, Chaonan; Wang, Xiaoquan; Gu, Min; Liu, Xiaowen; Hu, Shunlin; Liu, Xiufan

2017-11-30

H3 subtype avian influenza virus (AIV) poses a great threat to public health, and so investigating its epidemiology is of great importance. A novel reassortant H3N2 AIV strain was isolated from a live poultry market in eastern China. The strain's genes originated from H1N1, H3, and H7 AIVs. Thus, the genome information of the H3N2 isolate will help to investigate further the epidemiology of H3 subtype AIVs in China. Copyright © 2017 Sun et al.

China is closely monitoring an increase in infection with avian influenza A (H7N9) virus.

PubMed

Tang, Qi; Shao, Meiying; Xu, Lingzhong

2017-03-22

The fifth outbreak of human infection with avian influenza A (H7N9) virus has struck far and wide in China. The number of cases of infection with the avian influenza A (H7N9) suddenly increased in 2013-2014, but the number of cases reported this winter has exceeded the number reported in all previous seasons. Given this situation, the National Health and Family Planning Commission issued updated Chinese guidelines (2017 version) on diagnosis and treatment of infection with the avian influenza A (H7N9) virus on January 24, 2017. In addition, the Chinese Government closed many live poultry markets in urban and rural areas in a number of provinces and the Government has taken proactive measures to surveil, respond to, and prevent potential pandemics involving the avian influenza A (H7N9) virus.

Highly pathogenic avian influenza A(H7N9) virus, Tennessee, USA, March 2017

USDA-ARS?s Scientific Manuscript database

In March 2017, highly pathogenic avian influenza A(H7N9) was detected at 2 poultry farms in Tennessee, USA. Surveillance data and genetic analyses indicated multiple introductions of low pathogenicity avian influenza virus before mutation to high pathogenicity and interfarm transmission. Poultry sur...

Emergence and evolution of avian H5N2 influenza viruses in chickens in Taiwan.

PubMed

Lee, Chang-Chun David; Zhu, Huachen; Huang, Pei-Yu; Peng, Liuxia; Chang, Yun-Cheng; Yip, Chun-Hung; Li, Yao-Tsun; Cheung, Chung-Lam; Compans, Richard; Yang, Chinglai; Smith, David K; Lam, Tommy Tsan-Yuk; King, Chwan-Chuen; Guan, Yi

2014-05-01

Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003. H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the Eurasian gene pool. The

Emergence and Evolution of Avian H5N2 Influenza Viruses in Chickens in Taiwan

PubMed Central

Lee, Chang-Chun David; Zhu, Huachen; Huang, Pei-Yu; Peng, Liuxia; Chang, Yun-Cheng; Yip, Chun-Hung; Li, Yao-Tsun; Cheung, Chung-Lam; Compans, Richard; Yang, Chinglai; Smith, David K.; Lam, Tommy Tsan-Yuk

2014-01-01

ABSTRACT Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003. IMPORTANCE H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the

Highly Pathogenic Avian Influenza H5N1 Clade 2.3.2.1c Virus in Lebanon, 2016.

PubMed

El Romeh, Ali; Zecchin, Bianca; Fusaro, Alice; Ibrahim, Elias; El Bazzal, Bassel; El Hage, Jeanne; Milani, Adelaide; Zamperin, Gianpiero; Monne, Isabella

2017-06-01

We report the phylogenetic analysis of the first outbreak of H5N1 highly pathogenic avian influenza virus detected in Lebanon from poultry in April 2016. Our whole-genome sequencing analysis revealed that the Lebanese H5N1 virus belongs to genetic clade 2.3.2.1c and clusters with viruses from Europe and West Africa.

Genetic characterization of highly pathogenic avian influenza A H5N8 viruses isolated from wild birds in Egypt

PubMed Central

Kandeil, Ahmed; Kayed, Ahmed; Moatasim, Yassmin; Webby, Richard J.; McKenzie, Pamela P.

2017-01-01

A newly emerged H5N8 influenza virus was isolated from green-winged teal in Egypt during December 2016. In this study, we provide a detailed characterization of full genomes of Egyptian H5N8 viruses and some virological features. Genetic analysis demonstrated that the Egyptian H5N8 viruses are highly pathogenic avian influenza viruses. Phylogenetic analysis revealed that the genome of the Egyptian H5N8 viruses was related to recently characterized reassortant H5N8 viruses of clade 2.3.4.4 isolated from different Eurasian countries. Multiple peculiar mutations were characterized in the Egyptian H5N8 viruses, which probably permits transmission and virulence of these viruses in mammals. The Egyptian H5N8 viruses preferentially bound to avian-like receptors rather than human-like receptors. Also, the Egyptian H5N8 viruses were fully sensitive to amantadine and neuraminidase inhibitors. Chicken sera raised against commercial inactivated avian influenza-H5 vaccines showed no or very low reactivity with the currently characterized H5N8 viruses in agreement with the genetic dissimilarity. Surveillance of avian influenza in waterfowl provides early warning of specific threats to poultry and human health and hence should be continued. PMID:28721841

Genetic characterization of highly pathogenic avian influenza A H5N8 viruses isolated from wild birds in Egypt.

PubMed

Kandeil, Ahmed; Kayed, Ahmed; Moatasim, Yassmin; Webby, Richard J; McKenzie, Pamela P; Kayali, Ghazi; Ali, Mohamed A

2017-07-01

A newly emerged H5N8 influenza virus was isolated from green-winged teal in Egypt during December 2016. In this study, we provide a detailed characterization of full genomes of Egyptian H5N8 viruses and some virological features. Genetic analysis demonstrated that the Egyptian H5N8 viruses are highly pathogenic avian influenza viruses. Phylogenetic analysis revealed that the genome of the Egyptian H5N8 viruses was related to recently characterized reassortant H5N8 viruses of clade 2.3.4.4 isolated from different Eurasian countries. Multiple peculiar mutations were characterized in the Egyptian H5N8 viruses, which probably permits transmission and virulence of these viruses in mammals. The Egyptian H5N8 viruses preferentially bound to avian-like receptors rather than human-like receptors. Also, the Egyptian H5N8 viruses were fully sensitive to amantadine and neuraminidase inhibitors. Chicken sera raised against commercial inactivated avian influenza-H5 vaccines showed no or very low reactivity with the currently characterized H5N8 viruses in agreement with the genetic dissimilarity. Surveillance of avian influenza in waterfowl provides early warning of specific threats to poultry and human health and hence should be continued.

Emergence of novel clade 2.3.4 influenza A (H5N1) virus subgroups in Yunnan Province, China.

PubMed

Hu, Tingsong; Song, Jianling; Zhang, Wendong; Zhao, Huanyun; Duan, Bofang; Liu, Qingliang; Zeng, Wei; Qiu, Wei; Chen, Gang; Zhang, Yingguo; Fan, Quanshui; Zhang, Fuqiang

2015-07-01

From December 2013 to March 2014, a major wave of highly pathogenic avian influenza outbreak occurred in poultry in Yunnan Province, China. We isolated and characterized eight highly pathogenic avian influenza A (H5N1) viruses from poultry. Full genome influenza sequences and analyses have been performed. Sequence analyses revealed that they belonged to clade 2.3.4 but did not fit within the three defined subclades. The isolated viruses were provisional subclade 2.3.4.4e. The provisional subclade 2.3.4.4e viruses with six internal genes from avian influenza A (H5N2) viruses in 2013 were the novel reassortant influenza A (H5N1) viruses which were associated with the outbreak of H5N1 occurred in egg chicken farms in Yunnan Province. The HA genes were similar to subtype H5 viruses isolated from January to March of 2014 in Asia including H5N6 and H5N8. The NA genes were most closely related to A/chicken/Vietnam/NCVD-KA423/2013 (H5N1) from the subclade 2.3.2. The HI assay demonstrated a lack of antigenic relatedness between clades 2.3.4.4e and 2.3.4.1 (RE-5 vaccine strain) or 2.3.2.2 (RE-6 vaccine strain). Copyright © 2015 Elsevier B.V. All rights reserved.

The replication of Bangladeshi H9N2 avian influenza viruses carrying genes from H7N3 in mammals

PubMed Central

Shanmuganatham, Karthik K; Jones, Jeremy C; Marathe, Bindumadhav M; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Turner, Jasmine; Rabiul Alam, S M; Kamrul Hasan, M; Akhtar, Sharmin; Seiler, Patrick; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2016-01-01

H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans. PMID:27094903

The replication of Bangladeshi H9N2 avian influenza viruses carrying genes from H7N3 in mammals.

PubMed

Shanmuganatham, Karthik K; Jones, Jeremy C; Marathe, Bindumadhav M; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Turner, Jasmine; Rabiul Alam, S M; Kamrul Hasan, M; Akhtar, Sharmin; Seiler, Patrick; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2016-04-20

H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans.

Genetic and biological characterization of two novel reassortant H5N6 swine influenza viruses in mice and chickens.

PubMed

Li, Xuyong; Fu, Yuguang; Yang, Jiayun; Guo, Jing; He, Jijun; Guo, Jianhong; Weng, Shaoting; Jia, Yane; Liu, Bin; Li, Xiaoyang; Zhu, Qiyun; Chen, Hualan

2015-12-01

Novel H5N6 influenza A viruses have infected birds and human beings and caused four human clinical cases in China since 2014. The pig, as a mixing vessel, plays an important role for influenza virus reassortment and transmission. Towards this, routine surveillance for swine influenza in Guangdong province was conducted in 2014. In this study, we reported the biological characterization of two H5N6 influenza viruses isolated from healthy pigs in Guangdong province. Genetic analysis indicates that the two viruses are reassortants of 2.3.4.4 H5N1 and H6N6 avian influenza viruses with a high similarity to duck and human H5N6 influenza viruses isolated from Guangdong province. The data from chicken and mouse experiments show that the viruses are highly pathogenic in chickens and result in a systemic infection, and replicate in the mouse lung accompanying with a clinical inflammatory pathology. The results of the study demonstrate that the two H5N6 influenza viruses isolated from swine are the avian-originated viruses and have not adapted to swine population yet. However, they might keep evolving and pose a potential risk to public health and the continued surveillance of swine influenza should be strengthened. Copyright © 2015 Elsevier B.V. All rights reserved.

Sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses.

PubMed

Limsuwat, Nattavatchara; Suptawiwat, Ornpreya; Boonarkart, Chompunuch; Puthavathana, Pilaipan; Wiriyarat, Witthawat; Auewarakul, Prasert

2016-03-01

It was shown previously that human saliva has higher antiviral activity against human influenza viruses than against H5N1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic-acid-containing molecules. To further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza A and B virus, pandemic H1N1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and chicken saliva. Human saliva showed higher hemagglutination inhibition (HI) and neutralization (NT) titers against seasonal influenza A virus and the pandemic H1N1 viruses than against influenza B virus and most avian influenza viruses, except for H9N2 and H12N9 avian influenza viruses, which showed high HI and NT titers. To understand the nature of sialic-acid-containing anti-influenza factors in human saliva, α2,3- and α2,6-linked sialic acid was measured in human saliva samples using a lectin binding and dot blot assay. α2,6-linked sialic acid was found to be more abundant than α2,3-linked sialic acid, and a seasonal H1N1 influenza virus bound more efficiently to human saliva than an H5N1 virus in a dot blot analysis. These data indicated that human saliva contains the sialic acid type corresponding to the binding preference of seasonal influenza viruses.

Investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza A(H10N8) in Nanchang City, China.

PubMed

Ni, Xiansheng; He, Fenglan; Hu, Maohong; Zhou, Xianfeng; Wang, Bin; Feng, Changhua; Wu, Yumei; Li, Youxing; Tu, Junling; Li, Hui; Liu, Mingbin; Chen, Haiying; Chen, Shengen

2015-01-01

Multiple reassortment events within poultry and wild birds had resulted in the establishment of another novel avian influenza A(H10N8) virus, and finally resulted in human death in Nanchang, China. However, there was a paucity of information on the prevalence of avian influenza virus in poultry and wild birds in Nanchang area. We investigated avian influenza virus in poultry and wild birds from live poultry markets, poultry countyards, delivery vehicles, and wild-bird habitats in Nanchang. We analyzed 1036 samples from wild birds and domestic poultry collected from December 2013 to February 2014. Original biological samples were tested for the presence of avian influenza virus using specific primer and probe sets of H5, H7, H9, H10 and N8 subtypes by real-time RT-PCR. In our analysis, the majority (97.98%) of positive samples were from live poultry markets. Among the poultry samples from chickens and ducks, AIV prevalence was 26.05 and 30.81%, respectively. Mixed infection of different HA subtypes was very common. Additionally, H10 subtypes coexistence with N8 was the most prevalent agent during the emergence of H10N8. This event illustrated a long-term surveillance was so helpful for pandemic preparedness and response. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Avian influenza surveillance in domestic waterfowl and environment of live bird markets in Bangladesh, 2007-2012.

PubMed

Khan, Salah Uddin; Gurley, Emily S; Gerloff, Nancy; Rahman, Md Z; Simpson, Natosha; Rahman, Mustafizur; Haider, Najmul; Chowdhury, Sukanta; Balish, Amanda; Zaman, Rashid Uz; Nasreen, Sharifa; Chandra Das, Bidhan; Azziz-Baumgartner, Eduardo; Sturm-Ramirez, Katharine; Davis, C Todd; Donis, Ruben O; Luby, Stephen P

2018-06-20

Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns. We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments. We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012. Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses. Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype. The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl. Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples. Environmental samples tested positive for influenza A viruses throughout the year. Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry. Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them.

Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

PubMed Central

Havers, Fiona; Iuliano, A. Danielle; Davis, C. Todd; Sar, Borann; Sovann, Ly; Chin, Savuth; Corwin, Andrew L.; Vongphrachanh, Phengta; Douangngeun, Bounlom; Lindblade, Kim A.; Chittaganpitch, Malinee; Kaewthong, Viriya; Kile, James C.; Nguyen, Hien T.; Pham, Dong V.; Donis, Ruben O.; Widdowson, Marc-Alain

2015-01-01

During February 2013–March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013–May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely. PMID:25897654

H9N2 avian influenza transmission and antigenicity

USDA-ARS?s Scientific Manuscript database

Low pathogenic H9N2 avian influenza has become endemic in parts of Asia, the Middle East and North Africa causing respiratory disease with occasional mortality. The use of vaccination has become common to try and control the clinical disease, but vaccination has not been shown to be an effective er...

Virological and pathological characterization of an avian H1N1 influenza A virus.

PubMed

Koo, Bon-Sang; Kim, Hye Kwon; Song, Daesub; Na, Woonsung; Song, Min-Suk; Kwon, Jin Jung; Wong, Sook-San; Noh, Ji Yeong; Ahn, Min-Ju; Kim, Doo-Jin; Webby, Richard J; Yoon, Sun-Woo; Jeong, Dae Gwin

2018-05-01

Gene segments from avian H1N1 influenza A viruses have reassorted with other influenza viruses to generate pandemic strains over the past century. Nevertheless, little effort has been invested in understanding the characteristics of avian H1N1 influenza viruses. Here, we present the genome sequence and a molecular and virological characterization of an avian influenza A virus, A/wild bird/Korea/SK14/2014 (A/SK14, H1N1), isolated from migratory birds in South Korea during the winter season of 2014-2015. Full-genome sequencing and phylogenetic analysis revealed that the virus belongs to the Eurasian avian lineage. Although it retained avian-receptor binding preference, A/SK14 virus also exhibited detectable human-like receptor binding and was able to replicate in differentiated primary normal human bronchial epithelial cells. In animal models, A/SK14 virus was moderately pathogenic in mice, and virus was detected in nasal washes from inoculated guinea pigs, but not in direct-contact guinea pigs. Although A/SK14 showed moderate pathogenicity and no evidence of transmission in a mammalian model, our results suggest that the dual receptor specificity of A/SK14-like virus might allow for a more rapid adaptation to mammals, emphasizing the importance of further continuous surveillance and risk-assessment activities.

Experimental infection of dogs with highly pathogenic avian influenza virus (H5N8).

PubMed

Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; Tseren-Ochir, Erdene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Song, Chang-Seon

2017-08-31

During the highly pathogenic avian influenza (HPAI) H5N8 virus outbreak in Korea, a dog in layer farm contaminated by H5N8 was reported seropositive for HPAI H5N8. To investigate the possibility of adaptation and transmission of HPAI H5N8 to dogs, we experimentally inoculated dogs with H5N8. Viral genes were weakly detected in nasal swabs and seroconversions in inoculated and contact dogs. Although the H5N8 virus did not induced severe clinical signs to dogs, the results suggest that surveillance of farm dogs should continue as a species in which the avian influenza virus may acquire infectivity to mammals through frequent contact with the virus.

Highly pathogenic avian influenza virus subtype H5N1 in Mute swans in the Czech Republic.

PubMed

Nagy, Alexander; Machova, Jirina; Hornickova, Jitka; Tomci, Miroslav; Nagl, Ivan; Horyna, Bedrich; Holko, Ivan

2007-02-25

In order to determine the actual prevalence of avian influenza viruses (AIV) in wild birds in the Czech Republic extensive surveillance was carried out between January and April 2006. A total of 2101 samples representing 61 bird species were examined for the presence of influenza A by using PCR, sequencing and cultivation on chicken embryos. AIV subtype H5N1 was detected in 12 Mute swans (Cygnus olor). The viruses were determined as HPAI (highly pathogenic avian influenza) and the hemagglutinin sequence was closely similar to A/mallard/Italy/835/06 and A/turkey/Turkey/1194/05. Following the first H5N1 case, about 300 wild birds representing 33 species were collected from the outbreak region and tested for the presence of AIV without any positive result. This is the first report of highly pathogenic avian influenza subtype H5N1 in the Czech Republic. The potential role of swan as an effective vector of avian influenza virus is also discussed.

Protection against avian influenza H9N2 virus challenge by immunization with hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Meizhen; Fang Fang; Chen Yan

2006-05-19

Avian influenza viruses of H9N2 subtype are widely spread in avian species. The viruses have recently been transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. In this study, an avian influenza H9N2 virus strain (A/Chicken/Jiangsu/7/2002), isolated in Jiangsu Province, China, was used to infect BALB/c mice for adaptation. After five lung-to-lung passages, the virus was stably proliferated in a large quantity in the murine lung and caused the deaths of mice. In addition, we explored the protection induced by H9N2 virus hemagglutinin (HA)- and neuraminidase (NA)-expressing DNAs in BALB/c mice. Female BALB/c micemore » aged 6-8 weeks were immunized once or twice at a 3-week interval with HA-DNA and NA-DNA by electroporation, respectively, each at a dose of 3, 10 or 30 {mu}g. The mice were challenged with a lethal dose (40x LD{sub 5}) of influenza H9N2 virus four weeks after immunization once or one week after immunization twice. The protections of DNA vaccines were evaluated by the serum antibody titers, residual lung virus titers, and survival rates of the mice. The result showed that immunization once with not less than 10 {mu}g or twice with 3 {mu}g HA-DNA or NA-DNA provided effective protection against homologous avian influenza H9N2 virus.« less

Lemna (duckweed) expressed hemagglutinin from avian influenza H5N1 protects chickens against H5N1 high pathogenicity avian influenza virus challenge

USDA-ARS?s Scientific Manuscript database

In the last two decades, transgenic plants have been explored as safe and cost effective alternative expression platforms for producing recombinant proteins. In this study, a synthetic hemagglutinin (HA) gene from the high pathogenicity avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1)...

Histopathological characterization and shedding dynamics of guineafowl (Numida meleagris) intravenously infected with a H6N2 low pathogenicity Avian Influenza virus

USDA-ARS?s Scientific Manuscript database

Guineafowl of different ages were inoculated intravenously with an H6N2 wild waterfowl-origin low-pathogenicity type A avian influenza virus (LPAI). No evidence of clinical disease was observed. The examined infected birds had atrophy of the spleen, thymus, and cloacal bursa when compared to the n...

Highly Pathogenic Avian Influenza Virus (H5N8) Clade 2.3.4.4 Infection in Migratory Birds, Egypt.

PubMed

Selim, Abdullah A; Erfan, Ahmed M; Hagag, Naglaa; Zanaty, Ali; Samir, Abdel-Hafez; Samy, Mohamed; Abdelhalim, Ahmed; Arafa, Abdel-Satar A; Soliman, Mohamed A; Shaheen, Momtaz; Ibraheem, Essam M; Mahrous, Ibrahim; Hassan, Mohamed K; Naguib, Mahmoud M

2017-06-01

We isolated highly pathogenic avian influenza virus (H5N8) of clade 2.3.4.4 from the common coot (Fulica atra) in Egypt, documenting its introduction into Africa through migratory birds. This virus has a close genetic relationship with subtype H5N8 viruses circulating in Europe. Enhanced surveillance to detect newly emerging viruses is warranted.

Novel reassortant H10N7 avian influenza viruses isolated from chickens in Eastern China.

PubMed

Wu, Haibo; Lu, Rufeng; Wu, Xiaoxin; Peng, Xiaorong; Xu, Lihua; Cheng, Linfang; Lu, Xiangyun; Jin, Changzhong; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

2015-04-01

Since 2004, the H10N7 subtype avian influenza virus (AIV) has caused sporadic human infections with variable clinical symptoms world-wide. However, there is limited information pertaining to the molecular characteristics of H10N7 AIVs in China. To more fully characterize the genetic relationships between three novel H10N7 strains isolated from chickens in Eastern China and the strains isolated from birds throughout Asia, and to determine the pathogenicity of the H10N7 isolates in vivo. All eight gene segments from the Chinese H10N7 strains were sequenced and compared with AIV strains available in GenBank. The virulence of the three isolates was determined in chickens and mice. Three H10N7 subtype avian influenza viruses were isolated from chickens in live poultry markets in Eastern China in 2014: (1) A/chicken/Zhejiang/2C66/2014(H10N7) (ZJ-2C66), (2) A/chicken/Zhejiang/2CP2/2014(H10N7) (ZJ-2CP2), and (3) A/chicken/Zhejiang/2CP8/2014(H10N7) (ZJ-2CP8). Phylogenetic analysis indicated that the viruses contained genetic material from H10, H2, H7, and H3 AIV strains that were circulating at the same time. The reassortant H10N7 viruses were found to be minimally pathogenic in chickens and moderately pathogenic in mice. The viruses were able to replicate in mice without prior adaptation. These results suggest that H10N7 surveillance in poultry should be used as an early warning system for avian influenza outbreaks. The novel strains identified here may post a threat to human health in the future if they continue to circulate. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection and characterization of an H4N6 avian-lineage influenza A virus in pigs in the Midwestern United States

USDA-ARS?s Scientific Manuscript database

H4Nx viruses were reported in swine in Canada and China, but had not been recognized in swine in the USA. In late 2015, an avian-origin H4N6 influenza A virus was isolated from pigs in the United States during a routine diagnostic investigation of clinical respiratory disease in the herd. Serologica...

H7N9 and H5N1 avian influenza suitability models for China: accounting for new poultry and live-poultry markets distribution data.

PubMed

Artois, Jean; Lai, Shengjie; Feng, Luzhao; Jiang, Hui; Zhou, Hang; Li, Xiangping; Dhingra, Madhur S; Linard, Catherine; Nicolas, Gaëlle; Xiao, Xiangming; Robinson, Timothy P; Yu, Hongjie; Gilbert, Marius

2017-01-01

In the last two decades, two important avian influenza viruses infecting humans emerged in China, the highly pathogenic avian influenza (HPAI) H5N1 virus in the late nineties, and the low pathogenic avian influenza (LPAI) H7N9 virus in 2013. China is home to the largest population of chickens (4.83 billion) and ducks (0.694 billion), representing, respectively 23.1 and 58.6% of the 2013 world stock, with a significant part of poultry sold through live-poultry markets potentially contributing to the spread of avian influenza viruses. Previous models have looked at factors associated with HPAI H5N1 in poultry and LPAI H7N9 in markets. However, these have not been studied and compared with a consistent set of predictor variables. Significant progress was recently made in the collection of poultry census and live-poultry market data, which are key potential factors in the distribution of both diseases. Here we compiled and reprocessed a new set of poultry census data and used these to analyse HPAI H5N1 and LPAI H7N9 distributions with boosted regression trees models. We found a limited impact of the improved poultry layers compared to models based on previous poultry census data, and a positive and previously unreported association between HPAI H5N1 outbreaks and the density of live-poultry markets. In addition, the models fitted for the HPAI H5N1 and LPAI H7N9 viruses predict a high risk of disease presence for the area around Shanghai and Hong Kong. The main difference in prediction between the two viruses concerned the suitability of HPAI H5N1 in north-China around the Yellow sea (outlined with Tianjin, Beijing, and Shenyang city) where LPAI H7N9 has not spread intensely.

The T160A hemagglutinin substitution affects not only receptor binding property but also transmissibility of H5N1 clade 2.3.4 avian influenza virus in guinea pigs.

PubMed

Gu, Min; Li, Qunhui; Gao, Ruyi; He, Dongchang; Xu, Yunpeng; Xu, Haixu; Xu, Lijun; Wang, Xiaoquan; Hu, Jiao; Liu, Xiaowen; Hu, Shunlin; Peng, Daxin; Jiao, Xinan; Liu, Xiufan

2017-02-06

We generated and characterized site-directed HA mutants on the genetic backbone of H5N1 clade 2.3.4 virus preferentially binding to α-2,3 receptors in order to identify the key determinants in hemagglutinin rendering the dual affinity to both α-2,3 (avian-type) and α-2,6 (human-type) linked sialic acid receptors of the current clade 2.3.4.4 H5NX subtype avian influenza reassortants. The results show that the T160A substitution resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs, which could be considered as an important molecular marker for assessing pandemic potential of H5 subtype avian influenza isolates.

Novel H5N8 clade 2.3.4.4 highly pathogenic avian influenza virus in wild awuatic birds, Russia, 2016

USDA-ARS?s Scientific Manuscript database

H5N1 high pathogenicity avian influenza virus (HPAIV) emerged in 1996 in Guangdong China (Gs/GD) and has evolved into multiple genetic clades. Since 2008, HPAIV H5 clade 2.3.4 with N2, N5 and N8 neuraminidase subtypes have been identified in mainland China and outbreak of HPAIV H5N8 clade 2.3.4.4 ou...

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

PubMed

Kim, Shin-Hee

2018-03-09

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

PubMed Central

2018-01-01

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry. PMID:29522492

Avian Influenza H7N9/13 and H7N7/13: a Comparative Virulence Study in Chickens, Pigeons, and Ferrets

PubMed Central

Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P.; Starick, Elke; Harder, Timm

2014-01-01

ABSTRACT Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. IMPORTANCE This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk

Efficient replication and strong induction of innate immune responses by H9N2 avian influenza virus in human dendritic cells.

PubMed

Westenius, Veera; Mäkelä, Sanna M; Ziegler, Thedi; Julkunen, Ilkka; Österlund, Pamela

2014-12-01

Avian influenza A (H9N2) viruses have occasionally been identified in humans with upper respiratory tract infections. The novel H7N9/2013 virus identified in China shows that a low pathogenic avian influenza (LPAI) virus can be highly pathogenic in humans. Therefore, it is important to understand virus-host cell interactions and immune responses triggered by LPAI viruses in humans. We found that LPAI A/Hong Kong/1073/99 (H9N2) virus replicated efficiently in human dendritic cells (DCs). The H9N2 virus induced strong IFN gene expression although with different kinetics than seasonal influenza A/Beijing/353/89 (H3N2) virus. IFN inducible antiviral proteins were produced in H9N2 virus-infected cells at the same level as in H3N2 infection. The H9N2 virus was extremely sensitive to the antiviral actions of type I IFNs. These results indicate that the avian influenza H9N2 virus is inducing a strong antiviral IFN response in human DCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Low-Pathogenic Avian Influenza Viruses in Wild House Mice

PubMed Central

Shriner, Susan A.; VanDalen, Kaci K.; Mooers, Nicole L.; Ellis, Jeremy W.; Sullivan, Heather J.; Root, J. Jeffrey; Pelzel, Angela M.; Franklin, Alan B.

2012-01-01

Background Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. Methodology/Principal Findings We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus) caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID50 equivalents/mL) across all lung samples from seven days of sampling (three mice/day) ranged from 103.89 (H3N6) to 105.06 (H4N6) for the wild bird viruses and 102.08 (H6N2) to 102.85 (H4N8) for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p<0.05) higher concentrations of avian influenza RNA found in females compared with males. Conclusions/Significance Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics. PMID:22720076

[Prediction and evolution of B cell epitopes of hemagglutinin in human-infecting H6N1 avian influenza virus].

PubMed

Yang, Jianke; Yuan, Jian; Gao, Jiguang; Zhu, Xiaolei; Lin, Aiqin

2015-01-01

To predict B cell epitopes of hemagglutinin (HA) of human-infecting H6N1 avian influenza virus and analyze their evolutionary characteristics. The dataset was downloaded from GISAID and GenBank databases. And the linear and conformational B cell epitopes of HA were predicted separately by various bioinformatic software. Furthermore, the conservation, adaptation and other evolutionary characteristics were also analyzed by some bioinformatic means. Four linear epitopes (A, B, C and D) and two conformational epitopes (E and F) were obtained after consideration of multiple factors. And the C epitope and sites ( 41, 157, 186, 187) mutated easily, but the other epitopes were very conservative and the D epitope was the most conservative. Interestingly, the site 157 was identified under positive selection, suggesting that it may be a particularly important site to make the virus evade the attack from the host immune system. The HA of human-infecting H6N1 avian influenza virus has five conservative B cell epitopes (three linear and two conformational) and one site under positive selection. The findings would facilitate the vaccine development, virus control and pathogenesis understanding.

Avian influenza A (H7N9) virus infection in humans: epidemiology, evolution, and pathogenesis.

PubMed

Husain, Matloob

2014-12-01

New human influenza A virus strains regularly emerge causing seasonal epidemics and occasional pandemics. Lately, several zoonotic avian influenza A strains have been reported to directly infect humans. In early 2013, a novel avian influenza A virus (H7N9) strain was discovered in China to cause severe respiratory disease in humans. Since then, over 450 human cases of H7N9 infection have been discovered and 165 of them have died. Multiple epidemiological, phylogenetic, in vivo, and in vitro studies have been done to determine the origin and pathogenesis of novel H7N9 strain. This article reviews the literature related to the epidemiology, evolution, and pathogenesis of the H7N9 strain since its discovery in February 2013 till August 2014. The data available so far indicate that H7N9 was originated by a two-step reassortment process in birds and transmitted to humans through direct contact with live-bird markets. H7N9 is a low-pathogenic avian virus and contains several molecular signatures for adaptation in mammals. The severity of the respiratory disease caused by novel H7N9 virus in humans can be partly attributed to the age, sex, and underlying medical conditions of the patients. A universal influenza vaccine is not available, though several strain-specific H7N9 candidate vaccine viruses have been developed. Further, novel H7N9 virus is resistant to antiviral drug amantadine and some H7N9 isolates have acquired the resistance to neuraminidase-inhibitors. Therefore, constant surveillance and prompt control measures combined with novel research approaches to develop alternative and effective anti-influenza strategies are needed to overcome influenza A virus. Copyright © 2014 Elsevier B.V. All rights reserved.

The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains

PubMed Central

Wu, Gang; Zhang, Jinghui; Webster, Robert G.

2015-01-01

Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans. PMID:26208281

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

PubMed Central

Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S.; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo

2015-01-01

ABSTRACT Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool. IMPORTANCE Although natural infection of humans with an avian H3N8 influenza A virus has not yet been reported, this influenza A virus subtype has already crossed the species barrier. Therefore, we have examined the potential of H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our results demonstrated that avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation

Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine.

PubMed

Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo; Montoya, María

2015-11-01

Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool. Although natural infection of humans with an avian H3N8 influenza A virus has not yet been reported, this influenza A virus subtype has already crossed the species barrier. Therefore, we have examined the potential of H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our results demonstrated that avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Surprisingly, we

Unique Determinants of Neuraminidase Inhibitor Resistance among N3, N7, and N9 Avian Influenza Viruses.

PubMed

Song, Min-Suk; Marathe, Bindumadhav M; Kumar, Gyanendra; Wong, Sook-San; Rubrum, Adam; Zanin, Mark; Choi, Young-Ki; Webster, Robert G; Govorkova, Elena A; Webby, Richard J

2015-11-01

Human infections with avian influenza viruses are a serious public health concern. The neuraminidase (NA) inhibitors (NAIs) are the frontline anti-influenza drugs and are the major option for treatment of newly emerging influenza. Therefore, it is essential to identify the molecular markers of NAI resistance among specific NA subtypes of avian influenza viruses to help guide clinical management. NAI-resistant substitutions in NA subtypes other than N1 and N2 have been poorly studied. Here, we identified NA amino acid substitutions associated with NAI resistance among influenza viruses of N3, N7, and N9 subtypes which have been associated with zoonotic transmission. We applied random mutagenesis and generated recombinant influenza viruses carrying single or double NA substitution(s) with seven internal genes from A/Puerto Rico/8/1934 (H1N1) virus. In a fluorescence-based NA inhibition assay, we identified three categories of NA substitutions associated with reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir): (i) novel subtype-specific substitutions in or near the enzyme catalytic site (R152W, A246T, and D293N, N2 numbering), (ii) subtype-independent substitutions (E119G/V and/or D and R292K), and (iii) substitutions previously reported in other subtypes (Q136K, I222M, and E276D). Our data show that although some markers of resistance are present across NA subtypes, other subtype-specific markers can only be determined empirically. The number of humans infected with avian influenza viruses is increasing, raising concerns of the emergence of avian influenza viruses resistant to neuraminidase (NA) inhibitors (NAIs). Since most studies have focused on NAI-resistance in human influenza viruses, we investigated the molecular changes in NA that could confer NAI resistance in avian viruses grown in immortalized monolayer cells, especially those of the N3, N7, and N9 subtypes, which have caused human infections. We identified not only numerous NAI

Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice.

PubMed

Li, Yan; Xu, Jun; Shi, Weiqing; Chen, Cheng; Shao, Yan; Zhu, Limei; Lu, Wei; Han, XiaoDong

2016-10-28

The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza. We hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 10 4 MID 50 of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs. MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment. MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.

Quantifying Transmission of Highly Pathogenic and Low Pathogenicity H7N1 Avian Influenza in Turkeys

PubMed Central

Saenz, Roberto A.; Essen, Steve C.; Brookes, Sharon M.; Iqbal, Munir; Wood, James L. N.; Grenfell, Bryan T.; McCauley, John W.; Brown, Ian H.; Gog, Julia R.

2012-01-01

Outbreaks of avian influenza in poultry can be devastating, yet many of the basic epidemiological parameters have not been accurately characterised. In 1999–2000 in Northern Italy, outbreaks of H7N1 low pathogenicity avian influenza virus (LPAI) were followed by the emergence of H7N1 highly pathogenic avian influenza virus (HPAI). This study investigates the transmission dynamics in turkeys of representative HPAI and LPAI H7N1 virus strains from this outbreak in an experimental setting, allowing direct comparison of the two strains. The fitted transmission rates for the two strains are similar: 2.04 (1.5–2.7) per day for HPAI, 2.01 (1.6–2.5) per day for LPAI. However, the mean infectious period is far shorter for HPAI (1.47 (1.3–1.7) days) than for LPAI (7.65 (7.0–8.3) days), due to the rapid death of infected turkeys. Hence the basic reproductive ratio, is significantly lower for HPAI (3.01 (2.2–4.0)) than for LPAI (15.3 (11.8–19.7)). The comparison of transmission rates and are critically important in relation to understanding how HPAI might emerge from LPAI. Two competing hypotheses for how transmission rates vary with population size are tested by fitting competing models to experiments with differing numbers of turkeys. A model with frequency-dependent transmission gives a significantly better fit to experimental data than density-dependent transmission. This has important implications for extrapolating experimental results from relatively small numbers of birds to the commercial poultry flock size, and for how control, including vaccination, might scale with flock size. PMID:23028760

Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus

PubMed Central

Sun, Hailiang; Blackmon, Sherry; Yang, Guohua; Waters, Kaitlyn; Li, Tao; Tangwangvivat, Ratanaporn; Xu, Yifei; Shyu, Daniel; Wen, Feng; Cooley, Jim; Senter, Lucy; Lin, Xiaoxu; Jarman, Richard; Hanson, Larry; Webby, Richard

2017-01-01

ABSTRACT Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus (CIV) H3N2 (CIV-H3N2) and equine-origin CIV H3N8 (CIV-H3N8), are enzootic in the canine population. Dogs have been demonstrated to seroconvert in response to diverse IAVs, and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antiserum, we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting that there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2 × pandemic H1N1 (pdmH1N1) reassortants by characterizing their in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1, identifying some combinations that were more active than either parental virus complex. Using reverse genetics and fixing the CIV-H3N2 hemagglutinin (HA), we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high-growth phenotypes in vitro, and 13 of these replicated in mouse lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant was efficiently transmitted by contact but not by the airborne route and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs. IMPORTANCE IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained transmission into a human population with limited herd immunity. Dogs are a a potential mixing vessel for

Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.

PubMed

Sun, Hailiang; Blackmon, Sherry; Yang, Guohua; Waters, Kaitlyn; Li, Tao; Tangwangvivat, Ratanaporn; Xu, Yifei; Shyu, Daniel; Wen, Feng; Cooley, Jim; Senter, Lucy; Lin, Xiaoxu; Jarman, Richard; Hanson, Larry; Webby, Richard; Wan, Xiu-Feng

2017-11-01

Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus (CIV) H3N2 (CIV-H3N2) and equine-origin CIV H3N8 (CIV-H3N8), are enzootic in the canine population. Dogs have been demonstrated to seroconvert in response to diverse IAVs, and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antiserum, we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting that there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2 × pandemic H1N1 (pdmH1N1) reassortants by characterizing their in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1, identifying some combinations that were more active than either parental virus complex. Using reverse genetics and fixing the CIV-H3N2 hemagglutinin (HA), we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high-growth phenotypes in vitro , and 13 of these replicated in mouse lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant was efficiently transmitted by contact but not by the airborne route and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs. IMPORTANCE IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained transmission into a human population with limited herd immunity. Dogs are a a potential mixing vessel for avian

Avian influenza viruses (AIVs) H9N2 are in the course of reassorting into novel AIVs.

PubMed

Chang, Hui-Ping; Peng, Li; Chen, Liang; Jiang, Lu-Fang; Zhang, Zhi-Jie; Xiong, Cheng-Long; Zhao, Gen-Ming; Chen, Yue; Jiang, Qing-Wu

2018-05-01

In 2013, two episodes of influenza emerged in China and caused worldwide concern. A new H7N9 avian influenza virus (AIV) first appeared in China on February 19, 2013. By August 31, 2013, the virus had spread to ten provinces and two metropolitan cities. Of 134 patients with H7N9 influenza, 45 died. From then on, epidemics emerged sporadically in China and resulted in several victims. On November 30, 2013, a 73-year-old woman presented with an influenza-like illness. She developed multiple organ failure and died 9 d after the onset of disease. A novel reassortant AIV, H10N8, was isolated from a tracheal aspirate specimen that was obtained from the patient 7 d after onset. This case was the first human case of influenza A subtype H10N8. On 4 February, 2014, another death due to H10N8 avian influenza was reported in Jiangxi Province, China.

Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

PubMed Central

Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J.; Walsh, Douglas S.; Saunders, David L.

2014-01-01

We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity. PMID:24277784

Emergence in China of human disease due to avian influenza A(H10N8)--cause for concern?

PubMed

To, Kelvin K W; Tsang, Alan K L; Chan, Jasper F W; Cheng, Vincent C C; Chen, Honglin; Yuen, Kwok-Yung

2014-03-01

In December 2013, China reported the first human case of avian influenza A(H10N8). A 73-year-old female with chronic diseases who had visited a live poultry market succumbed with community-acquired pneumonia. While human infections with avian influenza viruses are usually associated with subtypes prevalent in poultries, A(H10N8) isolates were mostly found in migratory birds and only recently in poultries. Although not possible to predict whether this single intrusion by A(H10N8) is an accident or the start of another epidemic like the preceding A(H7N9) and A(H5N1), several features suggest that A(H10N8) is a potential threat to humans. Recombinant H10 could attach to human respiratory epithelium, and A(H10N4) virus could cause severe infections in minks and chickens. A(H10N8) viruses contain genetic markers for mammalian adaptation and virulence in the haemagglutinin (A135T, S138A[H3 numbering]), M1(N30D, T215A), NS1(P42S) and PB2(E627K) protein. Studies on this human A(H10N8) isolate will reveal its adaptability to humans. Clinicians should alert the laboratory to test for A(H5,6,7,9,10) viruses in patients with epidemiological exposure in endemic geographical areas especially when human influenza A(H1,3) and B are negative. Vigilant virological and serological surveillance for A(H10N8) in human, poultry and wild bird is important for following the trajectory of this emerging influenza virus. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Pathogenesis and transmission of H7 and H5 highly pathogenic avian influenza viruses in mallards including the recent intercontinental H5 viruses (H5N8 and H5N2)

USDA-ARS?s Scientific Manuscript database

Highly pathogenic avian influenza viruses (HPAIV’s) remain a threat to poultry worldwide. Avian influenza viruses, including HPAIV, are usually non-pathogenic for ducks and other wild aquatic birds, with the exception of Asian lineage H5N1, and recently H5N8, HPAIVs, which can cause moderate to sev...

Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017.

PubMed

Zhou, Lei; Tan, Yi; Kang, Min; Liu, Fuqiang; Ren, Ruiqi; Wang, Yali; Chen, Tao; Yang, Yiping; Li, Chao; Wu, Jie; Zhang, Hengjiao; Li, Dan; Greene, Carolyn M; Zhou, Suizan; Iuliano, A Danielle; Havers, Fiona; Ni, Daxin; Wang, Dayan; Feng, Zijian; Uyeki, Timothy M; Li, Qun

2017-08-01

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

Reassortant clade 2.3.4.4 Avian Influenza A(H5N6) Virus in a wild Mandarin Duck, South Korea, 2016

USDA-ARS?s Scientific Manuscript database

Highly pathogenic avian influenza viruses (HPAIV) have caused significant economic losses in the poultry industries and represents a serious threat to public health. H5N1 HPAIV was first detected in 1996 from a domestic goose in Guangdong China (Gs/GD) and has subsequently evolved into 10 geneticall...

Avian influenza H7N9/13 and H7N7/13: a comparative virulence study in chickens, pigeons, and ferrets.

PubMed

Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P; Starick, Elke; Harder, Timm; Beer, Martin

2014-08-01

Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk analysis of low

Probable Tiger-to-Tiger Transmission of Avian Influenza H5N1

PubMed Central

Thanawongnuwech, Roongroje; Amonsin, Alongkorn; Tantilertcharoen, Rachod; Damrongwatanapokin, Sudarat; Theamboonlers, Apiradee; Payungporn, Sunchai; Nanthapornphiphat, Kamonchart; Ratanamungklanon, Somchuan; Tunak, Eakchai; Songserm, Thaweesak; Vivatthanavanich, Veravit; Lekdumrongsak, Thawat; Kesdangsakonwut, Sawang; Tunhikorn, Schwann

2005-01-01

During the second outbreak of avian influenza H5N1 in Thailand, probable horizontal transmission among tigers was demonstrated in the tiger zoo. Sequencing and phylogenetic analysis of those viruses showed no differences from the first isolate obtained in January 2004. This finding has implications for influenza virus epidemiology and pathogenicity in mammals. PMID:15890122

H9N2 low pathogenic avian influenza in Pakistan (2012-2015)

USDA-ARS?s Scientific Manuscript database

Significant economic losses from deaths and decreased egg production have resulted from H9N2 low pathogenic avian influenza virus (LPAIV) infections in poultry across North Africa, the Middle East and Asia. The H9N2 LPAIVs have been endemic in Pakistani poultry since 1996, but no new viruses have be...

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A H5N1 viruses in ferrets.

PubMed

Pearce, Melissa B; Pappas, Claudia; Gustin, Kortney M; Davis, C Todd; Pantin-Jackwood, Mary J; Swayne, David E; Maines, Taronna R; Belser, Jessica A; Tumpey, Terrence M

2017-02-01

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A(H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. To better understand the pathogenesis associated with the continued diversification of clade 2A(H5N1) influenza viruses, we investigated the relative virulence of eleven human and poultry isolates collected from 2006 to 2013 by determining their ability to cause disease in the ferret model. Numerous clade 2 viruses, including a clade 2.2 avian isolate, a 2.2.2.1 human isolate, and two 2.2.1 human isolates, were found to be of low virulence in the ferret model, though lethality was detected following infection with one 2.2.1 human isolate. In contrast, three of six clade 2.3.2.1 avian isolates tested led to severe disease and death among infected ferrets. Clade 2.3.2.1b and 2.3.2.1c isolates, but not 2.3.2.1a isolates, were associated with ferret lethality. All A(H5N1) viruses replicated efficiently in the respiratory tract of ferrets regardless of their virulence and lethality. However, lethal isolates were characterized by systemic viral dissemination, including detection in the brain and enhanced histopathology in lung tissues. The finding of disparate virulence phenotypes between clade 2A(H5N1) viruses, notably differences between subclades of 2.3.2.1 viruses, suggests there are distinct molecular determinants present within the established subclades, the identification of which will assist in molecular-based surveillance and public health efforts against A(H5N1) viruses. Published by Elsevier Inc.

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A H5N1 viruses in ferrets

PubMed Central

Pearce, Melissa B.; Pappas, Claudia; Gustin, Kortney M.; Davis, C. Todd; Pantin-Jackwood, Mary J.; Swayne, David E.; Maines, Taronna R.; Belser, Jessica A.; Tumpey, Terrence M.

2017-01-01

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A(H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. To better understand the pathogenesis associated with the continued diversification of clade 2 A(H5N1) influenza viruses, we investigated the relative virulence of eleven human and poultry isolates collected from 2006 to 2013 by determining their ability to cause disease in the ferret model. Numerous clade 2 viruses, including a clade 2.2 avian isolate, a 2.2.2.1 human isolate, and two 2.2.1 human isolates, were found to be of low virulence in the ferret model, though lethality was detected following infection with one 2.2.1 human isolate. In contrast, three of six clade 2.3.2.1 avian isolates tested led to severe disease and death among infected ferrets. Clade 2.3.2.1b and 2.3.2.1c isolates, but not 2.3.2.1a isolates, were associated with ferret lethality. All A(H5N1) viruses replicated efficiently in the respiratory tract of ferrets regardless of their virulence and lethality. However, lethal isolates were characterized by systemic viral dissemination, including detection in the brain and enhanced histopathology in lung tissues. The finding of disparate virulence phenotypes between clade 2 A(H5N1) viruses, notably differences between subclades of 2.3.2.1 viruses, suggests there are distinct molecular determinants present within the established subclades, the identification of which will assist in molecular-based surveillance and public health efforts against A(H5N1) viruses. PMID:28038412

Reintroduction of highly pathogenic avian influenza A/H5N8 virus of clade 2.3.4.4. in Russia.

PubMed

Marchenko, Vasiliy Y; Susloparov, Ivan M; Komissarov, Andrey B; Fadeev, Artem; Goncharova, Nataliya I; Shipovalov, Andrey V; Svyatchenko, Svetlana V; Durymanov, Alexander G; Ilyicheva, Tatyana N; Salchak, Lyudmila K; Svintitskaya, Elena P; Mikheev, Valeriy N; Ryzhikov, Alexander B

2017-05-01

In the spring of 2016, a loss of wild birds was observed during the monitoring of avian influenza virus activity in the Republic of Tyva. That outbreak was caused by influenza H5N8 virus of clade 2.3.4.4. In the fall, viruses of H5N8 clade 2.3.4.4 were propagated in European countries. This paper presents some results of analysis of the virus strains isolated during the spring and fall seasons in 2016 in the Russian Federation. The investigated strains were highly pathogenic for mice, and some of their antigenic and genetic features differed from those of an H5N8 strain that circulated in 2014 in Russia.

Characterization of clade 2.3.4.4 highly pathogenic H5 avian influenza viruses in ducks and chickens.

PubMed

Sun, Honglei; Pu, Juan; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, George F; Liu, Xiufan; Liu, Jinhua

2016-01-01

Worldwide dissemination of reassortant variants of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses has posed a great threat to the poultry industry. Here, we systematically characterized the H5N2, H5N6 and H5N8 influenza viruses in poultry and compared them with those of previous clade 2.3.4 H5N1 virus. All the three H5 subtype reassortants caused systematic infection in ducks, and exhibited efficient direct transmission in ducks. All of them were highly pathogenic in chickens; however, the H5 reassortants have reduced virulence compared to the parental H5N1 virus. Antigenicity analysis revealed that the current vaccines that are widely used in China may fail to confer protection against the H5 reassortants. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic Diversity of Highly Pathogenic Avian Influenza A(H5N8/H5N5) Viruses in Italy, 2016-17.

PubMed

Fusaro, Alice; Monne, Isabella; Mulatti, Paolo; Zecchin, Bianca; Bonfanti, Lebana; Ormelli, Silvia; Milani, Adelaide; Cecchettin, Krizia; Lemey, Philippe; Moreno, Ana; Massi, Paola; Dorotea, Tiziano; Marangon, Stefano; Terregino, Calogero

2017-09-01

In winter 2016-17, highly pathogenic avian influenza A(H5N8) and A(H5N5) viruses of clade 2.3.4.4 were identified in wild and domestic birds in Italy. We report the occurrence of multiple introductions and describe the identification in Europe of 2 novel genotypes, generated through multiple reassortment events.

Patient-derived avian influenza A (H5N6) virus is highly pathogenic in mice but can be effectively treated by anti-influenza polyclonal antibodies.

PubMed

Pan, Weiqi; Xie, Haojun; Li, Xiaobo; Guan, Wenda; Chen, Peihai; Zhang, Beiwu; Zhang, Mincong; Dong, Ji; Wang, Qian; Li, Zhixia; Li, Shufen; Yang, Zifeng; Li, Chufang; Zhong, Nanshan; Huang, Jicheng; Chen, Ling

2018-06-13

Highly pathogenic avian influenza A (H5N6) virus has been circulating in poultry since 2013 and causes sporadic infections and fatalities in humans. Due to the re-occurrence and continuous evolution of this virus subtype, there is an urgent need to better understand the pathogenicity of the H5N6 virus and to identify effective preventative and therapeutic strategies. We established a mouse model to evaluate the virulence of H5N6 A/Guangzhou/39715/2014 (H5N6/GZ14), which was isolated from an infected patient. BALB/c mice were inoculated intranasally with H5N6/GZ14 and monitored for morbidity, mortality, cytokine production, lung injury, viral replication, and viral dissemination to other organs. H5N6/GZ14 is highly pathogenic and can kill 50% of mice at a very low infectious dose of 5 plaque-forming units (pfu). Infection with H5N6/GZ14 showed rapid disease progression, viral replication to high titers in the lung, a strongly induced pro-inflammatory cytokine response, and severe lung injury. Moreover, infectious H5N6/GZ14 could be detected in the heart and brain of the infected mice. We also demonstrated that anti-influenza polyclonal antibodies generated by immunizing rhesus macaques could protect mice from lethal infection. Our results provide insights into the pathogenicity of the H5N6 human isolate.

Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets

PubMed Central

Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan

2016-01-01

ABSTRACT Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. IMPORTANCE Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. PMID:27122581

Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets.

PubMed

Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

2016-07-15

Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Suspension culture process for H9N2 avian influenza virus (strain Re-2).

PubMed

Wang, Honglin; Guo, Suying; Li, Zhenguang; Xu, Xiaoqin; Shao, Zexiang; Song, Guicai

2017-10-01

H9N2 avian influenza virus has caused huge economic loss for the Chinese poultry industry since it was first identified. Vaccination is frequently used as a control method for the disease. Meanwhile suspension culture has become an important tool for the development of influenza vaccines. To optimize the suspension culture conditions for the avian influenza H9N2 virus (Re-2 strain) in Madin-Darby Canine Kidney (MDCK) cells, we studied the culture conditions for cell growth and proliferation parameters for H9N2 virus replication. MDCK cells were successfully cultured in suspension, from a small scale to industrial levels of production, with passage time and initial cell density being optimized. The influence of pH on the culture process in the reactor has been discussed and the process parameters for industrial production were explored via amplification of the 650L reactor. Subsequently, we cultivated cells at high cell density and harvested high amounts of virus, reaching 10log2 (1:1024). Furthermore an animal experiment was conducted to detect antibody. Compared to the chicken embryo virus vaccine, virus cultured from MDCK suspension cells can produce a higher amount of antibodies. The suspension culture process is simple and cost efficient, thus providing a solid foundation for the realization of large-scale avian influenza vaccine production.

Transmission and immunopathology of the avian influenza virus A/Anhui/1/2013 (H7N9) human isolate in three commonly commercialized avian species.

PubMed

Vidaña, B; Dolz, R; Busquets, N; Ramis, A; Sánchez, R; Rivas, R; Valle, R; Cordón, I; Solanes, D; Martínez, J; Majó, N

2018-05-01

H7N9 virus infection is a global concern, given that it can cause severe infection and mortality in humans. However, the understanding of H7N9 epidemiology, animal reservoir species and zoonotic risk remains limited. This work evaluates the pathogenicity, transmissibility and local innate immune response of three avian species harbouring different respiratory distribution of α2,6 and α2,3 SA receptors. Muscovy ducks, European quails and SPF chickens were intranasally inoculated with 10 5 embryo infectious dose (EID) 50 of the human H7N9 (A/Anhui/1/2013) influenza isolate. None of the avian species showed clinical signs or macroscopic lesions, and only mild microscopic lesions were observed in the upper respiratory tract of quail and chickens. Quail presented more severe histopathologic lesions and avian influenza virus (AIV) positivity by immunohistochemistry (IHC), which correlated with higher IL-6 responses. In contrast, Muscovy ducks were resistant to disease and presented higher IFNα and TLR7 response. In all species, viral shedding was higher in the respiratory than in the digestive tract. Higher viral shedding was observed in quail, followed by chicken and ducks, which presented similar viral titres. Efficient transmission was observed in all contact quail and half of the Muscovy ducks, while no transmission was observed between chicken. All avian species showed viral shedding in drinking water throughout infection. © 2017 Blackwell Verlag GmbH.

Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice.

PubMed

Park, Su-Jin; Kumar, Mukesh; Kwon, Hyeok-il; Seong, Rak-Kyun; Han, Kyudong; Song, Jae-min; Kim, Chul-Joong; Choi, Young-Ki; Shin, Ok Sarah

2015-11-18

Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses.

Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice

PubMed Central

Park, Su-Jin; Kumar, Mukesh; Kwon, Hyeok-il; Seong, Rak-Kyun; Han, Kyudong; Song, Jae-min; Kim, Chul-Joong; Choi, Young-Ki; Shin, Ok Sarah

2015-01-01

Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses. PMID:26576844

Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

PubMed

Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

2008-08-01

Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

Identification of four genotypes of H3N2 swine influenza virus in pigs from southern China.

PubMed

Chen, Jidang; Fu, Xinliang; Chen, Ye; He, Shuyi; Zheng, Yun; Cao, Zhenpeng; Yu, Wenxin; Zhou, Han; Su, Shuo; Zhang, Guihong

2014-10-01

In 2011, four H3N2 swine influenza viruses (SIVs) were isolated from nasal swabs of four pigs (800 nasal swabs were collected from pigs showing influenza-like symptoms) in Guangdong province, China. Four different genotypes of H3N2 appeared among pigs in southern China, including wholly human-like H3N2 viruses, intermediate (1975) double-reassortant human H3N2 viruses (resulting from reassortment between an early human lineage and a recent human lineage), recent double-reassortant human H3N2 viruses, and avian-like H3N2 viruses. Because pigs can support the reassortment of human and avian influenza viruses, our surveillance should be enhanced as a part of an overall pandemic preparedness plan.

Avian influenza H5N1 viral and bird migration networks in Asia

USGS Publications Warehouse

Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

Avian influenza H5N1 viral and bird migration networks in Asia

PubMed Central

Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia. PMID:25535385

Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus.

PubMed

Zhu, Henan; Hughes, Joseph; Murcia, Pablo R

2015-05-01

Influenza A viruses (IAVs) are maintained mainly in wild birds, and despite frequent spillover infections of avian IAVs into mammals, only a small number of viruses have become established in mammalian hosts. A new H3N2 canine influenza virus (CIV) of avian origin emerged in Asia in the mid-2000s and is now circulating in dog populations of China and South Korea, and possibly in Thailand. The emergence of CIV provides new opportunities for zoonotic infections and interspecies transmission. We examined 14,764 complete IAV genomes together with all CIV genomes publicly available since its first isolation until 2013. We show that CIV may have originated as early as 1999 as a result of segment reassortment among Eurasian and North American avian IAV lineages. We also identified amino acid changes that might have played a role in CIV emergence, some of which have not been previously identified in other cross-species jumps. CIV evolves at a lower rate than H3N2 human influenza viruses do, and viral phylogenies exhibit geographical structure compatible with high levels of local transmission. We detected multiple intrasubtypic and heterosubtypic reassortment events, including the acquisition of the NS segment of an H5N1 avian influenza virus that had previously been overlooked. In sum, our results provide insight into the adaptive changes required by avian viruses to establish themselves in mammals and also highlight the potential role of dogs to act as intermediate hosts in which viruses with zoonotic and/or pandemic potential could originate, particularly with an estimated dog population of ∼ 700 million. Influenza A viruses circulate in humans and animals. This multihost ecology has important implications, as past pandemics were caused by IAVs carrying gene segments of both human and animal origin. Adaptive evolution is central to cross-species jumps, and this is why understanding the evolutionary processes that shape influenza A virus genomes is key to elucidating

Characterization of highly pathogenic avian influenza H5N8 virus from Egyptian domestic waterfowl in 2017.

PubMed

Anis, Anis; AboElkhair, Mohammed; Ibrahim, Mahmoud

2018-08-01

In 2016, the highly pathogenic avian influenza (HPAI) H5N8 virus was detected in wild birds for the first time in Egypt. In the present study, we identified the HPAI virus H5N8 of clade 2.3.4.4 from domestic waterfowl in Egypt, suggesting its transmission to the domestic poultry from the migratory birds. Based on partial haemagglutinin gene sequence, this virus has a close genetic relationship with subtype H5N8 viruses circulating in Asia and Europe. Pathologically, H5N8 virus in hybrid duck induced nervous signs accompanied by encephalomalacia, haemorrhages, nonsuppurative encephalitis and nonsuppurative vasculitis. The granular layer of cerebellum showed multifocal areas of hydropic degeneration and the Purkinje cell neurons were necrotized or lost. Additionally, the lung, kidney and spleen were congested, and necrotizing pancreatitis was also observed. The co-circulation of both HPAI H5N1 and H5N8 subtypes with the low pathogenic avian influenza H9N2 subtype complicate the control of avian influenza in Egypt with the possibility of emergence of new reassortant viruses. Therefore, continuous monitoring with implementation of strict control measures is required. Research highlights HPAI H5N8 virus clade 2.3.4.4 was detected in domestic ducks and geese in Egypt in 2017. Phylogenetically, the virus was closely related to HPAI H5N8 viruses identified in Asia and Europe Nonsuppurative encephalitis was widely observed in HPAI H5N8 virus-infected ducks. Degeneration of the cerebellar granular layer was found in most of the brain tissues examined.

[Advances on epidemiological research of human infections with novel avian influenza A (H7N9) virus].

PubMed

Wang, Q M; Liu, S L; Chen, E F

2017-02-06

Human infections with novel avian influenza A(H7N9)virus was an emerging infectious disease discovered in March, 2013. As of June30, 2016, 770 cases of H7N9 were reported in worldwide including 315 deaths with 40.9% of high case fatality rate. Yangtze River Delta and Pearl River Delta were the high-prevalence area. Formerly, the cases of H7N9 were concentrated on the municipalities. However, most of the case-patients were from smaller cities or rural areas nowadays. The H7N9 human infections mainly occurred in winter and spring every waves as similar as seasonal and H5N1 human infections. Middle aged and old (the median age was 61 years) male patients were occupied the large proportion among the cases of H7N9. In addition, the phenomenon of the limited and unsustained human-to-human transmission were existed. At present, the 4 major epidemic waves had happened and human infections with novel avian influenza A (H7N9) virus could be outbreak regularly in China. In this paper, the pathogenic characteristics and disease distribution of H7N9 influenza A viruses were elaborated, with both transmission factors and control measures, which were helpful to provide the scientific evidence for prevention and control in H7N9avian influenza epidemic.

Avian influenza: a review.

PubMed

Thomas, Jennifer K; Noppenberger, Jennifer

2007-01-15

A review of the avian influenza A/H5N1 virus, including human cases, viral transmission, clinical features, vaccines and antivirals, surveillance plans, infection control, and emergency response plans, is presented. The World Health Organization (WHO) considers the avian influenza A/H5N1 virus a public health risk with pandemic potential. The next human influenza pandemic, if caused by the avian influenza A/H5N1 virus, is estimated to have a potential mortality rate of more than a hundred million. Outbreaks in poultry have been associated with human transmission. WHO has documented 258 confirmed human infections with a mortality rate greater than 50%. Bird-to-human transmission of the avian influenza virus is likely by the oral-fecal route. The most effective defense against an influenza pandemic would be a directed vaccine to elicit a specific immune response toward the strain or strains of the influenza virus. However, until there is an influenza pandemic, there is no evidence that vaccines or antivirals used in the treatment or prevention of such an outbreak would decrease morbidity or mortality. Surveillance of the bird and human populations for the highly pathogenic H5N1 is being conducted. Infection-control measures and an emergency response plan are discussed. Avian influenza virus A/H5N1 is a public health threat that has the potential to cause serious illness and death in humans. Understanding its pathology, transmission, clinical features, and pharmacologic treatments and preparing for the prevention and management of its outbreak will help avoid its potentially devastating consequences.

Emergence of fatal avian influenza in New England harbor seals

USGS Publications Warehouse

Anthony, S.J.; St. Leger, J. A.; Pugliares, K.; Ip, Hon S.; Chan, J.M.; Carpenter, Z.W.; Navarrete-Macias, I.; Sanchez-Leon, M.; Saliki, J.T.; Pedersen, J.; Karesh, W.; Daszak, P.; Rabadan, R.; Rowles, T.; Lipkin, W.I.

2012-01-01

From September to December 2011, 162 New England harbor seals died in an outbreak of pneumonia. Sequence analysis of postmortem samples revealed the presence of an avian H3N8 influenza A virus, similar to a virus circulating in North American waterfowl since at least 2002 but with mutations that indicate recent adaption to mammalian hosts. These include a D701N mutation in the viral PB2 protein, previously reported in highly pathogenic H5N1 avian influenza viruses infecting people. Lectin staining and agglutination assays indicated the presence of the avian-preferred SAα-2,3 and mammalian SAα-2,6 receptors in seal respiratory tract, and the ability of the virus to agglutinate erythrocytes bearing either the SAα-2,3 or the SAα-2,6 receptor. The emergence of this A/harbor seal/Massachusetts/1/2011 virus may herald the appearance of an H3N8 influenza clade with potential for persistence and cross-species transmission.

[Occupational exposure induced human transmissible highly pathogenic H5N1 avian influenza in one patient].

PubMed

Zhou, Hong-sheng; Liu, Jing-hu; Wang, Xiu-quan; Guo, Jiang-hua; Song, Xiao-lin

2007-03-01

To describe the clinical manifestations and lung imaging characteristics of the human transmissible highly pathogenic H5N1 avian influenza. The clinical manifestations and lung imaging characteristics of human transmissible highly pathogenic H5N1 avian influenza in one patient were reviewed and analyzed. The patient had the clear history of occupational exposure. The fever and symptoms of influenza were prominent at onset and associated with the symptoms of the digestive tract. The laboratory findings comprised the significant decrease of the white blood cell count and the lymphocyte number and the impairment of the liver function and the myocardial enzymes. The disease progressed rapidly and multiple organs including lung, heart, liver and kidneys were involved. It was ineffective to administer anti-fungal, anti-virus and anti-inflammation medicines. It was in vain to use mechanical ventilation and pneumothorax intubation and closed drainage as well as the support therapy. In the X-ray film, the lesions progressed quickly and changed diversely with absorption and development at the same time. The nasal and throat swabs and the gargle specimen were detected with RT-PCR and real time PCR by Chinese Center for Disease Control and Prevention. The results showed that both the specific HA and NA genes of the avian influenza virus H5N1 subtype were positive and in the same time a strain of avian influenza virus A/jiangxi/1/2005H5N1) was separated and obtained from the nasal and throat swabs. The autopsy showed that diffuse injury of alveolus in lungs, DIC and multiple organ injury. The human transmissible highly pathogenic H5N1 avian influenza is a lethal disease. The disease progresses rapidly with the absorption and development at the same time in the lungs and unfortunately there are no effective therapeutic measures. The prevention of the contagious disease for the occupationally exposed population should be emphasized.

A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

DOE PAGES

Zhang, Heng; de Vries, Robert  P.; Tzarum, Netanel; ...

2015-03-11

Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8 contains adaptations supporting human infection remains incompletely understood. In this paper, we investigated whether H10N8 HA can bind human receptors. Sialoside glycan microarray analysis showed that the H10 HA retains a strong preference for avian receptor analogs and negligible binding to human receptor analogs. Crystal structures of H10 HA with avian and human receptor analogs revealedmore » the basis for preferential recognition of avian-like receptors. Furthermore, introduction of mutations into the H10 receptor-binding site (RBS) known to convert other HA subtypes from avian to human receptor specificity failed to switch preference to human receptors. In conclusion, collectively these findings suggest that the current H10N8 human isolates are poorly adapted for efficient human-to-human transmission.« less

A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Heng; de Vries, Robert  P.; Tzarum, Netanel

Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8 contains adaptations supporting human infection remains incompletely understood. In this paper, we investigated whether H10N8 HA can bind human receptors. Sialoside glycan microarray analysis showed that the H10 HA retains a strong preference for avian receptor analogs and negligible binding to human receptor analogs. Crystal structures of H10 HA with avian and human receptor analogs revealedmore » the basis for preferential recognition of avian-like receptors. Furthermore, introduction of mutations into the H10 receptor-binding site (RBS) known to convert other HA subtypes from avian to human receptor specificity failed to switch preference to human receptors. In conclusion, collectively these findings suggest that the current H10N8 human isolates are poorly adapted for efficient human-to-human transmission.« less

Optical fiber sensor based on surface plasmon resonance for rapid detection of avian influenza virus subtype H6: Initial studies.

PubMed

Zhao, Xihong; Tsao, Yu-Chia; Lee, Fu-Jung; Tsai, Woo-Hu; Wang, Ching-Ho; Chuang, Tsung-Liang; Wu, Mu-Shiang; Lin, Chii-Wann

2016-07-01

A side-polished fiber optic surface plasmon resonance (SPR) sensor was fabricated to expose the core surface and then deposited with a 40 nm thin gold film for the near surface sensing of effective refractive index changes with surface concentration or thickness of captured avian influenza virus subtype H6. The detection surface of the SPR optical fiber sensor was prepared through the plasma modification method for binding a self-assembled monolayer of isopropanol chemically on the gold surface of the optical fiber. Subsequently, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide was activated to enable EB2-B3 monoclonal antibodies to capture A/chicken/Taiwan/2838V/00 (H6N1) through a flow injection system. The detection limit of the fabricated optical fiber sensor for A/chicken/Taiwan/2838V/00 was 5.14 × 10(5) EID50/0.1 mL, and the response time was 10 min on average. Moreover, the fiber optic sensor has the advantages of a compact size and low cost, thus rendering it suitable for online and remote sensing. The results indicated that the optical fiber sensor can be used for epidemiological surveillance and diagnosing of avian influenza subtype H6 rapidly. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistence of Avian Influenza Virus (H5N1) in Feathers Detached from Bodies of Infected Domestic Ducks ▿

PubMed Central

Yamamoto, Yu; Nakamura, Kikuyasu; Yamada, Manabu; Mase, Masaji

2010-01-01

Asian lineage highly pathogenic avian influenza virus (H5N1) continues to cause mortality in poultry and wild bird populations at a panzootic scale. However, little is known about its persistence in contaminated tissues derived from infected birds. We investigated avian influenza virus (H5N1) persistence in feathers detached from bodies of infected ducks to evaluate their potential risk for environmental contamination. Four-week-old domestic ducks were inoculated with different clades of avian influenza virus (H5N1). Feathers, drinking water, and feces were collected on day 3 postinoculation and stored at 4°C or 20°C. Viral persistence in samples was investigated for 360 days by virus isolation and reverse transcription-PCR. Infectious viruses persisted for the longest period in feathers, compared with drinking water and feces, at both 4°C and 20°C. Viral infectivity persisted in the feathers for 160 days at 4°C and for 15 days at 20°C. Viral titers of 104.3 50% egg infectious doses/ml or greater were detected for 120 days in feathers stored at 4°C. Viral RNA in feathers was more stable than the infectivity. These results indicate that feathers detached from domestic ducks infected with highly pathogenic avian influenza virus (H5N1) can be a source of environmental contamination and may function as fomites with high viral loads in the environment. PMID:20581177

Avian influenza virus (H5N1); effects of physico-chemical factors on its survival

PubMed Central

Shahid, Muhammad Akbar; Abubakar, Muhammad; Hameed, Sajid; Hassan, Shamsul

2009-01-01

Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI) H5N1 (local strain) virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light) and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon®-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda) agents. Harvested amnio-allantoic fluid (AAF) from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg) was subjected to haemagglutination (HA) and haemagglutination inhibition (HI) tests. H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C. Acidic pH (1, 3) and basic pH (11, 13) were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h), 7 and 9 (more than 24 h). UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy®), detergent (surf excel®) and alkali (caustic soda) destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV) outbreak. PMID:19327163

Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

PubMed Central

Kaplan, Bryan S.; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A.; Russell, Charles J.; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E.; Krauss, Scott

2016-01-01

ABSTRACT Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes

Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals.

PubMed

Kaplan, Bryan S; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A; Russell, Charles J; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E; Krauss, Scott; Webby, Richard J

2016-01-01

Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on

Pathogenicity and transmission of H5 highly pathogenic avian influenza clade 2.3.4.4 viruses (H5N8 and H5N2) in domestic waterfowl (Pekin ducks and Chinese geese)

USDA-ARS?s Scientific Manuscript database

Domestic ducks and geese are common backyard poultry in many countries, frequently in contact with wild waterfowl, which are natural reservoirs of avian influenza viruses and have played a key role in the spread of Asian-lineage H5N1 highly pathogenic avian influenza (HPAI). In late 2014, a reassor...

Inactivation of the novel avian influenza A (H7N9) virus under physical conditions or chemical agents treatment.

PubMed

Zou, Shumei; Guo, Junfeng; Gao, Rongbao; Dong, Libo; Zhou, Jianfang; Zhang, Ye; Dong, Jie; Bo, Hong; Qin, Kun; Shu, Yuelong

2013-09-15

In the spring of 2013, a novel avian-origin influenza A (H7N9) virus in Eastern China emerged causing human infections. Concerns that a new influenza pandemic could occur were raised. The potential effect of chemical agents and physical conditions on inactivation of the novel avian influenza H7N9 virus had not been assessed. To determine the inactivation effectiveness of the novel avian influenza A (H7N9) virus under various physical conditions and chemical treatments, two H7N9 viruses A/Anhui/1/2013 and A/Shanghai/1/2013 were treated by varied temperatures, ultraviolet light, varied pHs and different disinfectants. The viruses with 107.7 EID50 were exposed to physical conditions (temperature, ultraviolet light and pH) or treated with commercial chemical agents (Sodium Hypochlorite, Virkon®-S, and Ethanol) respectively. After these treatments, the viruses were inoculated in SPF embryonated chicken eggs, the allantoic fluid was collected after 72-96 hours culture at 35°C and tested by haemagglutination assay. Both of the tested viruses could tolerate conditions under 56°C for 15 minutes or 60°C for 5 minutes, but their infectivity was completely lost under 56°C for 30 minutes, 65°C for 10 minutes, 70°C, 75°C and 100°C for 1 minute. It was also observed that the H7N9 viruses lost their infectivity totally after exposure of ultraviolet light irradiation for 30 minutes or longer time. Additionally, the viruses were completely inactivated at pH less than 2 for 0.5 hour or pH 3 for 24 hours, however, viruses remained infectious under pH treatment of 4-12 for 24 hours. The viruses were totally disinfected when treated with Sodium Hypochlorite, Virkon®-S and Ethanol at recommended concentrations after only 5 minutes. The novel avian influenza A (H7N9) virus can be inactivated under some physical conditions or with chemical treatments, but they present high tolerance to moderately acidic or higher alkali conditions. The results provided the essential information

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.

PubMed

Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail

2016-02-01

The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

PubMed Central

Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter

2015-01-01

ABSTRACT The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions—T492S, N722D, R752K, and S1132F—were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCE Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011

PubMed Central

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi

2014-01-01

Objective Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. Methods We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. Results The overall seroprevalence was 6.1% (95% confidence interval: 4.6–8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. Discussion The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian–human transmission of influenza A(H5N1) in Viet Nam. PMID:25685601

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets

USDA-ARS?s Scientific Manuscript database

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A (H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, num...

A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.

PubMed

Rodriguez, Laura; Nogales, Aitor; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

2017-08-03

Canine influenza viruses (CIVs) cause a contagious respiratory disease in dogs. CIV subtypes include H3N8, which originated from the transfer of H3N8 equine influenza virus (EIV) to dogs; and the H3N2, which is an avian-origin virus adapted to infect dogs. Only inactivated influenza vaccines (IIVs) are currently available against the different CIV subtypes. However, the efficacy of these CIV IIVs is not optimal and improved vaccines are necessary for the efficient prevention of disease caused by CIVs in dogs. Since live-attenuated influenza vaccines (LAIVs) induce better immunogenicity and protection efficacy than IIVs, we have combined our previously described H3N8 and H3N2 CIV LAIVs to create a bivalent vaccine against both CIV subtypes. Our findings show that, in a mouse model of infection, the bivalent CIV LAIV is safe and able to induce, upon a single intranasal immunization, better protection than that induced by a bivalent CIV IIV against subsequent challenge with H3N8 or H3N2 CIVs. These protection results also correlated with the ability of the bivalent CIV LAIV to induce better humoral immune responses. This is the first description of a bivalent LAIV for the control and prevention of H3N8 and H3N2 CIV infections in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic evolution of H5 highly pathogenic avian influenza virus in domestic poultry in Vietnam between 2011 and 2013.

PubMed

Lee, Eun-Kyoung; Kang, Hyun-Mi; Kim, Kwang-Il; Choi, Jun-Gu; To, Thanh Long; Nguyen, Tho Dang; Song, Byung-Min; Jeong, Jipseol; Choi, Kang-Seuk; Kim, Ji-Ye; Lee, Hee-Soo; Lee, Youn-Jeong; Kim, Jae-Hong

2015-04-01

In spite of highly pathogenic avian influenza H5N1 vaccination campaigns for domestic poultry, H5N1 viruses continue to circulate in Vietnam. To estimate the prevalence of avian influenza virus in Vietnam, surveillance was conducted between November 2011 and February 2013. Genetic analysis of 312 highly pathogenic avian influenza H5 viruses isolated from poultry in Vietnam was conducted and possible genetic relationships with strains from neighboring countries were investigated. As previously reported, phylogenetic analysis of the avian influenza virus revealed two H5N1 HPAI clades that were circulating in Vietnam. Clade 1.1, related to Cambodian strains, was predominant in the southern provinces, while clade 2.3.2.1 viruses were predominant in the northern and central provinces. Sequence analysis revealed evidence of active genetic evolution. In the gene constellation of clade 2.3.2.1, genotypes A, B, and B(II) existed during the 2011/2012 winter season. In June 2012, new genotype C emerged by reassortment between genotype A and genotype B(II), and this genotype was predominant in 2013 in the northern and central provinces. Interestingly, enzootic Vietnamese clade 2.3.2.1C H5 virus subsequently reassorted with N2, which originated from wild birds, to generate H5N2 highly pathogenic avian influenza, which was isolated from duck in the northeast region. This investigation indicated that H5N1 outbreaks persist in Vietnam and cause genetic reassortment with circulating viruses. It is necessary to strengthen active influenza surveillance to eradicate highly pathogenic avian influenza viruses and sever the link between highly pathogenic avian influenza and other circulating influenza viruses. © 2015 Poultry Science Association Inc.

The occurrence of avian influenza A subtype H6N2 in commercial layer flocks in Southern California (2000-02): clinicopathologic findings.

PubMed

Kinde, Hailu; Read, Deryck H; Daft, Barbara M; Hammarlund, Marion; Moore, Janet; Uzal, Francisco; Mukai, Jenee; Woolcock, Peter

2003-01-01

Between February 2000 and February 2002, the California Animal Health and Food Safety Laboratory System diagnosed 26 cases of low-pathogenic H6N2 avian influenza from 12 commercial egg-laying farms. The most common gross and histologic lesions observed in infected chickens were fibrinous yolk peritonitis, salpingitis, oophoritis, and nephritis. Edema of the mesentery of the oviduct and pale, swollen kidneys were also observed. Mortality in infected flocks ranged from 0.25% to 3%, and egg production dropped 7% to 40%.

Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.

PubMed

Rabinowitz, P; Perdue, M; Mumford, E

2010-06-01

Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.

Fluorescence biosensor based on CdTe quantum dots for specific detection of H5N1 avian influenza virus

NASA Astrophysics Data System (ADS)

Hoa Nguyen, Thi; Dieu Thuy Ung, Thi; Hien Vu, Thi; Tran, Thi Kim Chi; Quyen Dong, Van; Khang Dinh, Duy; Liem Nguyen, Quang

2012-09-01

This report highlights the fabrication of fluorescence biosensors based on CdTe quantum dots (QDs) for specific detection of H5N1 avian influenza virus. The core biosensor was composed of (i) the highly luminescent CdTe/CdS QDs, (ii) chromatophores extracted from bacteria Rhodospirillum rubrum, and (iii) the antibody of β-subunit. This core part was linked to the peripheral part of the biosensor via a biotin-streptavidin-biotin bridge and finally connected to the H5N1 antibody to make it ready for detecting H5N1 avian influenza virus. Detailed studies of each constituent were performed showing the image of QDs-labeled chromatophores under optical microscope, proper photoluminescence (PL) spectra of CdTe/CdS QDs, chromatophores and the H5N1 avian influenza viruses.

Evolutionary dynamics of avian influenza A H7N9 virus across five waves in mainland China, 2013-2017.

PubMed

Xiang, Dan; Pu, Zhiqing; Luo, Tingting; Guo, Fucheng; Li, Xiaobing; Shen, Xuejuan; Irwin, David M; Murphy, Robert W; Liao, Ming; Shen, Yongyi

2018-05-25

Since its emergence in March 2013, novel avian influenza A H7N9 virus has triggered five epidemics of human infections in China. This raises concerns about the pandemic threat of this quickly evolving H7N9 subtype for humans. In this study, we evaluated all available genomes for H7N9 and H9N2 influenza A viruses. Our assessment discovered that H7N9 of the 1st wave had the lowest nucleotide diversity, which then experienced substantial and rapid population expansion from a small founder population. From the 2nd wave, their nucleotide diversity increased quickly, indicating that H7N9 viruses had acquired larger populations and mutations after their initial emergence in 2013. After the phylogeographic divergence in the 2nd wave, although the HA and NA genes from different regions differed, compared to previous epidemics, the evolving H7N9 viruses in the 5th wave lost most of their previous clades. The highly pathogenic avian influenza (HPAI) H7N9 viruses in the 5th wave clustered together, and clustered close to the low pathogenic avian influenza (LPAI) virus isolated from the Pearl River Delta in the 3rd and 4th waves. This result supports the origin of HPAI H7N9 viruses was in the Pearl River Delta. In the 5th wave, although both HPAI and LPAI H7N9 viruses were isolated from the Pearl River Delta, their HA and NA genes were phylogenetically distinct. Copyright © 2018. Published by Elsevier Ltd.

Outbreak patterns of the novel avian influenza (H7N9)

NASA Astrophysics Data System (ADS)

Pan, Ya-Nan; Lou, Jing-Jing; Han, Xiao-Pu

2014-05-01

The attack of novel avian influenza (H7N9) in East China caused a serious health crisis and public panic. In this paper, we empirically analyze the onset patterns of human cases of the novel avian influenza and observe several spatial and temporal properties that are similar to other infectious diseases. More specifically, using the empirical analysis and modeling studies, we find that the spatio-temporal network that connects the cities with human cases along the order of outbreak timing emerges two-regime-power-law edge-length distribution, indicating the picture that several islands with higher and heterogeneous risk straggle in East China. The proposed method is applicable to the analysis of the spreading situation in the early stage of disease outbreak using quite limited dataset.

Environmental Sampling for Avian Influenza A(H7N9) in Live-Poultry Markets in Guangdong, China

PubMed Central

Kang, Min; He, Jianfeng; Song, Tie; Rutherford, Shannon; Wu, Jie; Lin, Jinyan; Huang, Guofeng; Tan, Xiaohua; Zhong, Haojie

2015-01-01

Background To provide an increased understanding of avian influenza A(H7N9) activity in live-poultry market in space and time and hence improve H7N9 epidemic control, an ongoing environmental sampling program in multiple live-poultry markets across Guangdong, China was conducted during March 2013–June 2014. Methods A total of 625 live-poultry markets throughout 21 prefecture areas took part in the study. A total of 10 environmental sites in markets for sampling were identified to represent 4 different poultry-related activity areas. At least 10 environmental samples were collected from each market every month. The real time RT-PCR was performed to detect the avian influenza A(H7N9) virus. Field survey was conducted to investigate the sanitation status of live-poultry markets. Results There were 109 human infections with H7N9 avian influenza in Guangdong, of which 37 (34%) died. A total of 18741 environmental swabs were collected and subjected to real-time RT-PCR test, of which 905(4.83%) were found positive for H7N9 virus. There were 201 (32.16%) markets affected by H7N9 in 16 prefecture areas. The detection of H7N9 virus in markets spiked in winter months. 63.33% markets (38/60) had no physical segregation for poultry holding, slaughter or sale zones. Closing live-poultry market significantly decreased the H7N9 detection rate from 14.83% (112/755) to 1.67% (5/300). Conclusions This study indicates the importance of live-poultry market surveillance based on environmental sampling for H7N9 Avian Influenza control. Improving live-poultry market management and sanitation and changing consumer practices are critical to reduce the risk of H7N9 infection. PMID:25933138

Environmental Sampling for Avian Influenza A(H7N9) in Live-Poultry Markets in Guangdong, China.

PubMed

Kang, Min; He, Jianfeng; Song, Tie; Rutherford, Shannon; Wu, Jie; Lin, Jinyan; Huang, Guofeng; Tan, Xiaohua; Zhong, Haojie

2015-01-01

To provide an increased understanding of avian influenza A(H7N9) activity in live-poultry market in space and time and hence improve H7N9 epidemic control, an ongoing environmental sampling program in multiple live-poultry markets across Guangdong, China was conducted during March 2013-June 2014. A total of 625 live-poultry markets throughout 21 prefecture areas took part in the study. A total of 10 environmental sites in markets for sampling were identified to represent 4 different poultry-related activity areas. At least 10 environmental samples were collected from each market every month. The real time RT-PCR was performed to detect the avian influenza A(H7N9) virus. Field survey was conducted to investigate the sanitation status of live-poultry markets. There were 109 human infections with H7N9 avian influenza in Guangdong, of which 37 (34%) died. A total of 18741 environmental swabs were collected and subjected to real-time RT-PCR test, of which 905(4.83%) were found positive for H7N9 virus. There were 201 (32.16%) markets affected by H7N9 in 16 prefecture areas. The detection of H7N9 virus in markets spiked in winter months. 63.33% markets (38/60) had no physical segregation for poultry holding, slaughter or sale zones. Closing live-poultry market significantly decreased the H7N9 detection rate from 14.83% (112/755) to 1.67% (5/300). This study indicates the importance of live-poultry market surveillance based on environmental sampling for H7N9 Avian Influenza control. Improving live-poultry market management and sanitation and changing consumer practices are critical to reduce the risk of H7N9 infection.

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus.

PubMed

Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

2010-06-02

A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

Genetic Diversity of Highly Pathogenic Avian Influenza A(H5N8/H5N5) Viruses in Italy, 2016–17

PubMed Central

Monne, Isabella; Mulatti, Paolo; Zecchin, Bianca; Bonfanti, Lebana; Ormelli, Silvia; Milani, Adelaide; Cecchettin, Krizia; Lemey, Philippe; Moreno, Ana; Massi, Paola; Dorotea, Tiziano; Marangon, Stefano; Terregino, Calogero

2017-01-01

In winter 2016–17, highly pathogenic avian influenza A(H5N8) and A(H5N5) viruses of clade 2.3.4.4 were identified in wild and domestic birds in Italy. We report the occurrence of multiple introductions and describe the identification in Europe of 2 novel genotypes, generated through multiple reassortment events. PMID:28661831

Global dynamic analysis of a H7N9 avian-human influenza model in an outbreak region.

PubMed

Chen, Yongxue; Wen, Yongxian

2015-02-21

In 2013 in China a new type of avian influenza virus, H7N9, began to infect humans and had aroused severe fatality in the infected humans. We know that the spread is from poultry to humans, and the H7N9 avian influenza is low pathogenic in the poultry world but highly pathogenic in the human world, but the transmission mechanism is unclear. Since it has no signs of human-to-human transmission and outbreaks are isolated in some cities in China, in order to investigate the transmission mechanism of human infection with H7N9 avian influenza, an eco-epidemiological model in an outbreak region is proposed and analyzed dynamically. Researches and reports show that gene mutation makes the new virus be capable of infecting humans, therefore the mutation factor is taken into account in the model. The global dynamic analysis is conducted, different thresholds are identified, persistence and global qualitative behaviors are obtained. The impact of H7N9 avian influenza on the people population is concerned. Finally, the numerical simulations are carried out to support the theoretical analysis and to investigate the disease control measures. It seems that we may take people׳s hygiene and prevention awareness factor as a significant policy to achieve the aim of both the disease control and the economic returns. Copyright © 2014 Elsevier Ltd. All rights reserved.

Continuing evolution of H9N2 avian influenza virus in South Korea

USDA-ARS?s Scientific Manuscript database

The H9N2 low pathogenic avian influenza (LPAI) has caused great economic losses in Korean poultry industry since the first outbreak in 1996. Although the hemagglutinin gene of early H9N2 viruses were closely related to Chinese Y439-like lineage virus, it evolved into a unique Korean lineage after ...

Avian influenza viruses in humans.

PubMed

Malik Peiris, J S

2009-04-01

Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

Overview of avian influenza.

PubMed

Khare, Shashi; Agarwal, Ramesh; Singh, Ranjana; Lal, Shiv

2006-07-01

The current outbreak of H5N 1 avian influenza affecting an unprecedented number of countries is a cause of concern worldwide. As on 26th June, 2006 outbreaks in poultry or wild birds have been reported from 54 countries. In India the first outbreak of avian influenza virus Awas reported in Navapur district in Maharashtra in February 2006 followed by detection of H5N1 in a neighbouring district of Gujarat. No case of human infection has yet been reported in India. Avian influenza virus belongs to influenza type A which is a part of family orthomyxoviridae. Transmission occurs by direct or indirect contact. Clinical symptoms on human is of typical influenza like. Laboratory investigations involves a number of tests confirming diagnosis of avian influenza. The treatment includes general supportive and antiviral therapy with oseltamivir. Prevention and control strategies can held to minimise the public health risk to highly pathogenic avian influenza. There are some dos and don'ts for the community which should be strictly followed.

Development and evaluation of a real-time RT-PCR assay for detection of a novel avian influenza A (H5N6) virus.

PubMed

Zhang, Rusheng; Yao, Dong; Chen, Jingfang; Ye, Wen; Ou, Xinhua; Chen, Tianmu; Sun, Biancheng

2018-07-01

As of Aug 25, 2017, 17 incidences of human infection and 6 deaths due to the novel H5N6 virus have been reported in China. Genetic analysis of the viral genome revealed that this reassortant virus is highly pathogenic to poultry, and that the virus has a risk of transmission to humans. Accordingly, the development of a rapid, sensitive, and specific molecular diagnostic assay is critical for public health. In this study, a real-time reverse-transcription PCR (RT-PCR) assay was developed to specifically detect the novel H5N6 virus, with primer pairs targeting the hemagglutinin and neuraminidase gene sequences of this virus. RNA was extracted from throat swab specimens from patients with influenza-like illness (ILIs), and environmental samples were collected from live poultry markets (LPMs) for H5N6 virus detection by real-time RT-PCR. The method was demonstrated to enable specific detection of the avian H5N6 virus, with no cross-reactivity with seasonal influenza viruses (H1N1, H1N1 pdm09, H3N2 or B); H5N1, H7N9, H9N2 viruses; or other human respiratory viruses. The detection limit of the assay was 1.0 × 10 1 copies per reaction for N6 and 1.0 × 10 2 copies per reaction for H5 assays. The assay is a powerful tool for rapid, sensitive, and specific detection of H5N6 virus infection in specimens derived from humans, animals, and the environment. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014.

PubMed

Thuy, Duong Mai; Peacock, Thomas P; Bich, Vu Thi Ngoc; Fabrizio, Thomas; Hoang, Dang Nguyen; Tho, Nguyen Dang; Diep, Nguyen Thi; Nguyen, Minh; Hoa, Le Nguyen Minh; Trang, Hau Thi Thu; Choisy, Marc; Inui, Ken; Newman, Scott; Trung, Nguyen Vu; van Doorn, Rogier; To, Thanh Long; Iqbal, Munir; Bryant, Juliet E

2016-10-01

Despite their classification as low pathogenicity avian influenza viruses (LPAIV), A/H9N2 viruses cause significant losses in poultry in many countries throughout Asia, the Middle East and North Africa. To date, poultry surveillance in Vietnam has focused on detection of influenza H5 viruses, and there is limited understanding of influenza H9 epidemiology and transmission dynamics. We determined prevalence and diversity of influenza A viruses in chickens from live bird markets (LBM) of 7 northern Vietnamese provinces, using pooled oropharyngeal swabs collected from October to December 2014. Screening by real time RT-PCR revealed 1207/4900 (24.6%) of pooled swabs to be influenza A virus positive; overall prevalence estimates after accounting for pooling (5 swabs/pools) were 5.8% (CI 5.4-6.0). Subtyping was performed on 468 pooled swabs with M gene Ct<26. No influenza H7 was detected; 422 (90.1%) were H9 positive; and 22 (4.7%) were H5 positive. There was no evidence was of interaction between H9 and H5 virus detection rates. We sequenced 17 whole genomes of A/H9N2, 2 of A/H5N6, and 11 partial genomes. All H9N2 viruses had internal genes that clustered with genotype 57 and were closely related to Chinese human isolates of A/H7N9 and A/H10N8. Using a nucleotide divergence cutoff of 98%, we identified 9 distinct H9 genotypes. Phylogenetic analysis suggested multiple introductions of H9 viruses to northern Vietnam rather than in-situ transmission. Further investigations of H9 prevalence and diversity in other regions of Vietnam are warranted to assess H9 endemicity elsewhere in the country. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Highly pathogenic avian influenza virus (H5N1) isolated from whooper swans, Japan.

PubMed

Uchida, Yuko; Mase, Masaji; Yoneda, Kumiko; Kimura, Atsumu; Obara, Tsuyoshi; Kumagai, Seikou; Saito, Takehiko; Yamamoto, Yu; Nakamura, Kikuyasu; Tsukamoto, Kenji; Yamaguchi, Shigeo

2008-09-01

On April 21, 2008, four whooper swans were found dead at Lake Towada, Akita prefecture, Japan. Highly pathogenic avian influenza virus of the H5N1 subtype was isolated from specimens of the affected birds. The hemagglutinin (HA) gene of the isolate belongs to clade 2.3.2 in the HA phylogenetic tree.

Replication and Immunogenicity of Swine, Equine, and Avian H3 Subtype Influenza Viruses in Mice and Ferrets

PubMed Central

Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James; Cheng, Xing; Jin, Hong

2013-01-01

Since it is difficult to predict which influenza virus subtype will cause an influenza pandemic, it is important to prepare influenza virus vaccines against different subtypes and evaluate the safety and immunogenicity of candidate vaccines in preclinical and clinical studies prior to a pandemic. In addition to infecting humans, H3 influenza viruses commonly infect pigs, horses, and avian species. We selected 11 swine, equine, and avian H3 influenza viruses and evaluated their kinetics of replication and ability to induce a broadly cross-reactive antibody response in mice and ferrets. The swine and equine viruses replicated well in the upper respiratory tract of mice. With the exception of one avian virus that replicated poorly in the lower respiratory tract, all of the viruses replicated in mouse lungs. In ferrets, all of the viruses replicated well in the upper respiratory tract, but the equine viruses replicated poorly in the lungs. Extrapulmonary spread was not observed in either mice or ferrets. No single virus elicited antibodies that cross-reacted with viruses from all three animal sources. Avian and equine H3 viruses elicited broadly cross-reactive antibodies against heterologous viruses isolated from the same or other species, but the swine viruses did not. We selected an equine and an avian H3 influenza virus for further development as vaccines. PMID:23576512

Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

PubMed

Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

2011-06-01

Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

Modification of the Hemagglutinin Cleavage Site Allows Indirect Activation of Avian Influenza Virus H9N2 by Bacterial Staphylokinase

PubMed Central

Tse, Longping V.; Whittaker, Gary R.

2015-01-01

Influenza H9N2 is considered to be a low pathogenicity avian influenza (LPAI) virus that commonly infects avian species and can also infect humans. In 1996, the influenza virus, A/chicken/Korea/MS96-CE6/1996/H9N2 (MS96) was isolated from an outbreak in multiple farms in South Korea that resulted in upwards of 30% mortality in infected chickens, with the virus infecting a number of extrapulmonary tissues, indicating internal spread. However, in experimental infections, complete recovery of specific pathogen free (SPF) chickens occurred. Such a discrepancy indicated an alternative pathway for MS96 virus to gain virulence in farmed chickens. A key determinant of influenza pathogenesis is the susceptibility of the viral hemagglutinin (HA) to proteolytic cleavage/activation. Here, we identified that an amino acid substitution, Ser to Tyr found at the P2 position of the MS96 HA cleavage site optimizes cleavage by the protease plasmin (Pm). Importantly, we identified that certain Staphylococcus sp. are able to cleave and activate MS96 HA by activating plasminogen (Plg) to plasmin by use of a virulence factor, staphylokinase. Overall, these studies provide an in-vitro mechanism for bacterially mediated enhancement of influenza activation, and allow insight into the microbiological mechanisms underlying the avian influenza H9N2 outbreak in Korea in1996. PMID:25841078

Genetic and antigenic characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in the center part of Vietnam.

PubMed

Chu, Duc-Huy; Okamatsu, Masatoshi; Matsuno, Keita; Hiono, Takahiro; Ogasawara, Kohei; Nguyen, Lam Thanh; Van Nguyen, Long; Nguyen, Tien Ngoc; Nguyen, Thuy Thu; Van Pham, Dong; Nguyen, Dang Hoang; Nguyen, Tho Dang; To, Thanh Long; Van Nguyen, Hung; Kida, Hiroshi; Sakoda, Yoshihiro

2016-08-30

A total of 3,045 environmental samples and oropharyngeal and cloacal swabs from apparently healthy poultry have been collected at three live bird markets (LBMs) at which practices were applied to reduce avian influenza (AI) virus transmission (intervention LBMs) and six conventional LBMs (non-intervention LBMs) in Thua Thien Hue province in 2014 to evaluate the efficacy of the intervention LBMs. The 178 AI viruses, including H3 (19 viruses), H4 (2), H5 (8), H6 (30), H9 (114), and H11 (5), were isolated from domestic ducks, muscovy ducks, chickens, and the environment. The prevalence of AI viruses in intervention LBMs (6.1%; 95% CI: 5.0-7.5) was similar to that in non-intervention LBMs (5.6%; 95% CI: 4.5-6.8; χ(2)=0.532; df=1; P=0.53) in the study area. Eight H5N6 highly pathogenic avian influenza (HPAI) viruses were isolated from apparently healthy ducks, muscovy ducks, and an environmental sample in an intervention LBM. The hemagglutinin genes of the H5N6 HPAI viruses belonged to the genetic clade 2.3.4.4, and the antigenicity of the H5N6 HPAI viruses differed from the H5N1 HPAI viruses previously circulating in Vietnam. Phylogenetic and antigenic analyses of the H6 and H9 viruses isolated in both types of LBMs revealed that they were closely related to the viruses isolated from domestic birds in China, Group II of H6 viruses and Y280 lineage of H9 viruses. These results indicate that the interventions currently applied in LBMs are insufficient to control AI. A risk analysis should be conducted to identify the key factors contributing to AI virus prevalence in intervention LBMs. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel highly pathogenic H5N8 avian influenza virus isolated from a wild duck in China.

PubMed

Fan, Shengtao; Zhou, Lichen; Wu, Di; Gao, Xiaolong; Pei, Enle; Wang, Tianhou; Gao, Yuwei; Xia, Xianzhu

2014-11-01

Migrating wild birds are considered natural reservoirs of influenza viruses and serve as a potential source of novel influenza strains in humans and livestock. During routine avian influenza surveillance conducted in eastern China, a novel H5N8 (SH-9) reassortant influenza virus was isolated from a mallard duck in China. blast analysis revealed that the HA, NA, PB1, PA, NP, and M segments of SH-9 were most closely related to the corresponding segments of A/duck/Jiangsu/k1203/2010 (H5N8). The SH-9 virus preferentially recognized avian-like influenza virus receptors and was highly pathogenic in mice. Our results suggest that wild birds could acquire the H5N8 virus from breeding ducks and spread the virus via migratory bird flyways. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Human infection of novel avian influenza A(H7N4) virus.

PubMed

Tong, Xue-Cheng; Weng, Shan-Shan; Xue, Feng; Wu, Xing; Xu, Tian-Min; Zhang, Wen-Hong

2018-06-10

Multiple reassortant strains of novel, highly pathogenic avian influenza A have recently emerged and spread over the world. Here we report on a 68-year-old woman in Jiangsu, China, with influenza A(H7N4) infection and associated illness, which strongly demonstrating the ability of the virus to spread from animals to humans and thus emphasizing the importance of continuous surveillance of the emerging viruses. Copyright © 2018. Published by Elsevier Ltd.

Antigenic and Molecular Characterization of Avian Influenza A(H9N2) Viruses, Bangladesh

PubMed Central

Shanmuganatham, Karthik; Feeroz, Mohammed M.; Jones-Engel, Lisa; Smith, Gavin J.D.; Fourment, Mathieu; Walker, David; McClenaghan, Laura; Alam, S.M. Rabiul; Hasan, M. Kamrul; Seiler, Patrick; Franks, John; Danner, Angie; Barman, Subrata; McKenzie, Pamela; Krauss, Scott; Webby, Richard J.

2013-01-01

Human infection with avian influenza A(H9N2) virus was identified in Bangladesh in 2011. Surveillance for influenza viruses in apparently healthy poultry in live-bird markets in Bangladesh during 2008–2011 showed that subtype H9N2 viruses are isolated year-round, whereas highly pathogenic subtype H5N1 viruses are co-isolated with subtype H9N2 primarily during the winter months. Phylogenetic analysis of the subtype H9N2 viruses showed that they are reassortants possessing 3 gene segments related to subtype H7N3; the remaining gene segments were from the subtype H9N2 G1 clade. We detected no reassortment with subtype H5N1 viruses. Serologic analyses of subtype H9N2 viruses from chickens revealed antigenic conservation, whereas analyses of viruses from quail showed antigenic drift. Molecular analysis showed that multiple mammalian-specific mutations have become fixed in the subtype H9N2 viruses, including changes in the hemagglutinin, matrix, and polymerase proteins. Our results indicate that these viruses could mutate to be transmissible from birds to mammals, including humans. PMID:23968540

Vaccine protection of poultry against H5 clade 2.3.4.4 highly pathogenic avian influenza

USDA-ARS?s Scientific Manuscript database

Following the 2014-2015 outbreaks of H5N2 and H5N8 (clade 2.3.4.4) highly pathogenic avian influenza (HPAI) in the U.S., studies were performed to identify vaccines with potential to be used as a control mechanism in the event of future outbreaks. We tested both inactivated and recombinant vaccine...

Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents.

PubMed

Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

2014-09-01

Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Avian Influenza Virus A (H5N1), Detected through Routine Surveillance, in Child, Bangladesh

PubMed Central

Alamgir, A.S.M.; Sultana, Rebecca; Islam, M. Saiful; Rahman, Mustafizur; Fry, Alicia M.; Shu, Bo; Lindstrom, Stephen; Nahar, Kamrun; Goswami, Doli; Haider, M. Sabbir; Nahar, Sharifun; Butler, Ebonee; Hancock, Kathy; Donis, Ruben O.; Davis, Charles T.; Zaman, Rashid Uz; Luby, Stephen P.; Uyeki, Timothy M.; Rahman, Mahmudur

2009-01-01

We identified avian influenza virus A (H5N1) infection in a child in Bangladesh in 2008 by routine influenza surveillance. The virus was of the same clade and phylogenetic subgroup as that circulating among poultry during the period. This case illustrates the value of routine surveillance for detection of novel influenza virus. PMID:19751601

Novel Reassortant H5N6 Influenza A Virus from the Lao People's Democratic Republic Is Highly Pathogenic in Chickens.

PubMed

Butler, Jeffrey; Stewart, Cameron R; Layton, Daniel S; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P; Rootes, Christina L; Gough, Tamara J; Rohringer, Andreas; Peck, Grantley R; Fardy, Sarah J; Karpala, Adam J; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y K; Bean, Andrew G D; Bingham, John; Williams, David T

2016-01-01

Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People's Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations.