A Novel #Reassortant #Avian #H7N6 #Influenza Virus Is Transmissible in Guinea Pigs via Respiratory #Droplets (Front Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Microbiol. 2019 Jan 22;10:18. doi: 10.3389/fmicb.2019.00018. eCollection 2019.

A Novel Reassortant Avian H7N6 Influenza Virus Is Transmissible in Guinea Pigs via Respiratory Droplets.

Zhao Z1,2, Liu L1, Guo Z2, Zhang C2, Wang Z2, Wen G1, Zhang W1, Shang Y1, Zhang T1, Jiao Z1, Chen L3, Zhang C3, Cui H3, Jin M4, Wang C2, Luo Q1, Shao H1.

Author information: 1 Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China. 2 Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China. 3 College of Veterinary Medicine, Hebei Agricultural University, Baoding, China. 4 College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

 

Abstract

Since 2013, H7N9 and H5N6 avian influenza viruses (AIVs) have caused sporadic human infections and deaths and continued to circulate in the poultry industry. Since 2014, H7N6 viruses which might be reassortants of H7N9 and H5N6 viruses, have been isolated in China. However, the biological properties of H7N6 viruses are unknown. Here, we characterize the receptor binding preference, pathogenicity and transmissibility of a H7N6 virus A/chicken/Hubei/00095/2017(H7N6) (abbreviated HB95), and a closely related H7N9 virus, A/chicken/Hubei/00093/2017(H7N9) (abbreviated HB93), which were isolated from poultry in Hubei Province, China, in 2017. Phylogenetic analyses demonstrated that the hemagglutinin (HA) gene of HB95 is closely related to those of HB93 and human-origin H7N9 viruses, and that the neuraminidase (NA) gene of HB95 shared the highest nucleotide similarity with those of H5N6 viruses. HB95 and HB93 had binding affinity for human-like α2, 6-linked sialic acid receptors and were virulent in mice without prior adaptation. In addition, in guinea pig model, HB93 was transmissible by direct contact, but HB95 was transmissible via respiratory droplets. These results revealed the potential threat to public health posed by H7N6 influenza viruses and emphasized the need for continued surveillance of the circulation of this subtype in poultry.

KEYWORDS: avian H7N6 influenza A virus; pathogenicity; reassortment; receptor binding; transmissibility

PMID: 30723462 PMCID: PMC6349713 DOI: 10.3389/fmicb.2019.00018 Free PMC Article

Keywords: Avian Influenza; H7N9; H5N6; H7N6; Reassortant strain; Animal models.

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A 113-amino-acid #truncation at the #NS1 C-terminus is a determinant for viral #replication of #H5N6 #avian #influenza virus in vitro and in vivo (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Nov;225:6-16. doi: 10.1016/j.vetmic.2018.09.004. Epub 2018 Sep 13.

A 113-amino-acid truncation at the NS1 C-terminus is a determinant for viral replication of H5N6 avian influenza virus in vitro and in vivo.

Cui X1, Ji Y1, Wang Z1, Du Y1, Guo H1, Wang L1, Chen H2, Zhu Q3.

Author information: 1 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, PR China. 2 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, PR China. 3 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, PR China. Electronic address: zhuqiyun@caas.cn.

 

Abstract

Virulence of highly pathogenic avian influenza viruses (AIV) is determined by multiple genes and their encoded proteins. In particular, the nonstructural protein 1 (NS1) of viruses is a multifunctional protein that plays an important role in type I interferon (IFN) antagonism, pathogenicity, and determining viral host range. Naturally-occurring truncation or mutation of NS1 during virus evolution attenuates viral replication and pathogenicity, but the mechanisms underlying this phenomenon remain poorly understood. In the present study, we rescued an H5N6 AIV harboring a 113-amino-acid (aa) truncated NS1 at the C-terminus that had previously naturally occurred in an H3N8 equine influenza virus (designated as rHN109 NS1/112). The replication and pathogenicity of the rescued and parental viruses were then assessed in vitro in cells and in vivo in chickens and mice. Replication of rHN109 NS1/112 virus was significantly attenuated in various cells compared to its parental virus. The attenuation of rHN109 NS1/112 virus was subsequently clarified by investigating the effects on IFN and apoptosis signaling pathways via multiple experiments. The results indicated that the 113-aa truncation of NS1 impairs viral inhibition of IFN production and enhances cellular apoptosis in avian and mammalian cells. Animal studies further indicated that replication of the rHN109 NS1/112 virus is remarkably attenuated in chickens. The results of this study improve our understanding of C-terminal region function for NS1 proteins of influenza viruses.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS: Apoptosis; H5N6 AIV; Interferon; NS1; Replication

PMID: 30322535 DOI: 10.1016/j.vetmic.2018.09.004 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N6; Poultry.

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#Serosurveillance of #avian #influenza A/ #H5N6 virus #infection in #poultry #farmers, Gyeonggi Province, Republic of #Korea, 2016-2017 (Int J Infect Dis., abstract)

[Source: International Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2018 Oct;75:49-51. doi: 10.1016/j.ijid.2018.08.002. Epub 2018 Aug 7.

Serosurveillance of avian influenza A/H5N6 virus infection in poultry farmers, Gyeonggi Province, Republic of Korea, 2016-2017.

Ryu S1, Kim CK2, Kim K3, Woo SH2, Chun BC4.

Author information: 1 Division of Infectious Disease Control, Gyeonggi Provincial Government, Suwon, Republic of Korea; Department of Epidemiology and Health Informatics, Graduate School of Public Health, Korea University, Seoul, Republic of Korea. Electronic address: gentryu@onehealth.or.kr. 2 Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea. 3 Division of Viral Diseases Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea. 4 Department of Epidemiology and Health Informatics, Graduate School of Public Health, Korea University, Seoul, Republic of Korea; Department of Preventive Medicine, Korea University College of Medicine, Seoul, Republic of Korea.

 

Abstract

OBJECTIVES:

Between November 20, 2016 and April 17, 2017, outbreaks of highly pathogenic avian influenza (HPAI) A/H5N6 occurred on poultry farms in Gyeonggi Province in the Republic of Korea. A serosurvey was conducted among poultry farmers to identify the transmission of HPAI A/H5N6 virus to humans.

METHODS:

A descriptive study of 870 poultry farmers in Gyeonggi Province in Korea was conducted during the 2016-2017 outbreaks. Serological testing was performed using a microneutralization (MN) assay for antibodies against influenza A/duck/ES2/Korea/2016 virus, which has antigenic properties similar to those of the HPAI A/H5N6 virus that caused this poultry outbreak.

RESULTS:

Overall, 523 exposed poultry farmers were assessed by serological testing. Consequently, all tested negative for HPAI A/H5N6 virus via MN assay.

CONCLUSIONS:

Based on serological assays, no transmission of HPAI A/H5N6 to humans was identified in this study cohort. Additional studies should be conducted to determine the possibility of poultry-to-human transmission of HPAI A/H5N6.

Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

KEYWORDS: Avian influenza; H5N6; Korea; Poultry; Transmission

PMID: 30096358 DOI: 10.1016/j.ijid.2018.08.002

Keywords: Avian Influenza; H5N6; Human; Serosurveys; S. Korea.

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#Preclinical evaluation of the efficacy of an #H5N8 #vaccine candidate (IDCDC-RG43A) in mouse and ferret models for #pandemic preparedness (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2018 Nov 27. pii: S0264-410X(18)31589-5. doi: 10.1016/j.vaccine.2018.11.064. [Epub ahead of print]

Preclinical evaluation of the efficacy of an H5N8 vaccine candidate (IDCDC-RG43A) in mouse and ferret models for pandemic preparedness.

Jeong JH1, Kim EH1, Lloren KKS1, Kwon JJ1, Kwon HI1, Ahn SJ1, Kim YI1, Choi WS1, Si YJ1, Lee OJ1, Han HJ2, Baek YH1, Song MS3, Choi YK4, Kim CJ5.

Author information: 1 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. 2 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea; Research & Development Center, Green Cross Corporation, Yongin, Republic of Korea; Research & Development Center, Green Cross Wellbeing Corporation, Seongnam, Republic of Korea. 3 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. Electronic address: songminsuk@chungbuk.ac.kr. 4 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. Electronic address: choiki55@chungbuk.ac.kr. 5 College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: cjkim@cnu.ac.kr.

 

Abstract

Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra-clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 µg/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus.

KEYWORDS: H5N8 pre-pandemic vaccine; Immunogenicity; Preclinical evaluation; Protective efficacy

PMID: 30502069 DOI: 10.1016/j.vaccine.2018.11.064

Keywords: Avian Influenza; Pandemic Influenza; Pandemic Preparedness; Vaccines; H5N1; H5N6; H5N8.

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#Phylogenetic variations of highly pathogenic #H5N6 #avian #influenza viruses isolated from #wildbirds in the Izumi plain, #Japan during the 2016/17 winter season (Transbound Emerg Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transbound Emerg Dis. 2018 Nov 30. doi: 10.1111/tbed.13087. [Epub ahead of print]

Phylogenetic variations of highly pathogenic H5N6 avian influenza viruses isolated from wild birds in the Izumi plain, Japan during the 2016/17 winter season.

Ozawa M1,2,3, Matsuu A2,3, Khalil AMA1,3, Nishi N1, Tokorozaki K4, Masatani T2,3, Horie M2,3, Okuya K1, Ueno K1, Kuwahara M5, Toda S4.

Author information: 1 Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan. 2 Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Kagoshima, Japan. 3 United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Yamaguchi, Japan. 4 Kagoshima Crane Conservation Committee, Izumi, Kagoshima, Japan. 5 Matsuoka Research Institute for Science, Koganei, Tokyo, Japan.

 

Abstract

During the 2016/2017 winter season, we isolated 33 highly pathogenic avian influenza viruses (HPAIVs) of H5N6 subtype and three low pathogenic avian influenza viruses (LPAIVs) from debilitated or dead wild birds, duck feces, and environmental water samples collected in the Izumi plain, an overwintering site for migratory birds in Japan. Genetic analyses of the H5N6 HPAIV isolates revealed previously unreported phylogenetic variations in the PB2, PB1, PA, and NS gene segments and allowed us to propose two novel genotypes for the contemporary H5N6 HPAIVs. In addition, analysis of the four gene segments identified close phylogenetic relationships between our three LPAIV isolates and the contemporary H5N6 HPAIV isolates. Our results implied the co-circulation and co-evolution of HPAIVs and LPAIVs within the same wild bird populations, thereby highlighting the importance of avian influenza surveillance targeting not only for HPAIVs, but also for LPAIVs.

This article is protected by copyright. All rights reserved.

KEYWORDS: H5N6 subtype; highly pathogenic avian influenza virus; phylogenetic variations

PMID: 30499632 DOI: 10.1111/tbed.13087

Keywords: Avian Influenza; H5N6; Wild Birds; Japan.

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T160A #mutation-induced deglycosylation at site 158 in #HA is a critical determinant of the dual #RB properties of clade 2.3.4.4 #H5NX subtype #avian #influenza viruses (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Apr;217:158-166. doi: 10.1016/j.vetmic.2018.03.018. Epub 2018 Mar 17.

T160A mutation-induced deglycosylation at site 158 in hemagglutinin is a critical determinant of the dual receptor binding properties of clade 2.3.4.4 H5NX subtype avian influenza viruses.

Gao R1, Gu M2, Liu K1, Li Q1, Li J1, Shi L1, Li X1, Wang X2, Hu J2, Liu X2, Hu S2, Chen S2, Peng D3, Jiao X3, Liu X4.

Author information: 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China. 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. 3 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Most clade 2.3.4.4 H5NX subtype avian influenza viruses possess a T160A amino acid substitution in the hemagglutinin (HA) protein that has been shown to affect the receptor binding properties of a clade 2.3.4 H5N1 virus. However, the effect of this single site mutation on the HA backbone of clade 2.3.4.4 H5NX viruses remains unclear. In this study, two H5N6 field isolates possessing HA-160A with dual α-2,3 and α-2,6 receptor binding properties (Y6 virus) and HA-160T with α-2,3 receptor binding affinity (HX virus), respectively, were selected to generate HA mutants containing all of the internal genes from A/PR8/H1N1 virus for comparative investigation. We found that the Y6-P-160A and RHX-P-160A viruses each with 160A in the HA resulting in loss of glycosylation at site 158 exhibited binding to the two receptor types, whereas the RY6-P-160T and HX-P-160T viruses each with 160T in the HA displayed selective binding to α-2,3 receptors only. In addition, differences were noted in the replication of these four H5N6 recombinants in avian and mammalian cells, as well as in their pathogenicity in mice. The contribution of deglycosylation at site 158 to the acquisition of human-like receptors was further verified in H5N2, H5N5 and H5N8 reassortants. Therefore, we conclude that the lack of glycosylation at site 158 induced by the T160A mutation in HA is a critical determinant for the dual receptor binding properties of clade 2.3.4.4 H5NX viruses. This new insight may be helpful in assessing the pandemic potential of novel H5 isolates.

KEYWORDS: 158; Clade 2.3.4.4; Glycosylation; H5NX; Receptor

PMID: 29615249 DOI: 10.1016/j.vetmic.2018.03.018 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; H5N5; H5N6; H5N8; Reassortant Strain.

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#Human #infections with #avian #influenza viruses in mainland #China: A particular #risk for southeastern China (J Infect., abstract)

[Source: Journal of Infection, full page: (LINK). Abstract, edited.]

Human infections with avian influenza viruses in mainland China: A particular risk for southeastern China

Bin Xiang, Wenxian Zhu, Renrong You, Libin Chen, Yaling Li, Qiuyan Lin, Ming Liao, Tao Ren

DOI: https://doi.org/10.1016/j.jinf.2017.05.002

Published online: May 11, 2017 – Accepted:May 4, 2017

 

Abstract

As reported recently in this Journal, human infections with different subtypes of avian influenza viruses (AIVs) including H5N1, H5N6, H7N9, H10N8 and H9N2 have been identified in mainland China from 2005 to 2017.1–4Since the first H5N1 human case was confirmed in Hunan province in December 2005, a total of 46 human cases were reported in mainland China, of which 29 cases were fatal; while human infections with H5N6 virus was firstly documented in Sichuan province on March 3, 2014, 11 of 16 patients have been fatal (Table S1).

© 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Keywords: Avian Influenza; China; Human; H5N1; H5N6; H7N9; H10N8; H9N2.

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