#Genetic Characterization and #Zoonotic Potential of Highly Pathogenic #Avian #Influenza Virus A( #H5N6 / #H5N5), #Germany, 2017–2018 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Dispatch

Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017–2018

Anne Pohlmann1, Donata Hoffmann1, Christian Grund, Susanne Koethe, Daniela Hüssy, Simone M. Meier, Jacqueline King, Jan Schinköthe, Reiner Ulrich, Timm Harder, and Martin Beer

Author affiliations: Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany (A. Pohlmann, D. Hoffmann, C. Grund, S. Koethe, J. King, J. Schinköthe, R. Ulrich, T. Harder, M. Beer); Institute of Virology and Immunology, Mittelhäusern, Switzerland (D. Hüssy); Vetsuisse Faculty Zurich, Zurich, Switzerland (S.M. Meier)

 

Abstract

We genetically characterized highly pathogenic avian influenza virus A(H5N6) clade 2.3.4.4b isolates found in Germany in 2017–2018 and assessed pathogenicity of representative H5N5 and H5N6 viruses in ferrets. These viruses had low pathogenicity; however, continued characterization of related isolates is warranted because of their high potential for reassortment.

Keywords: Avian Influenza; H5N5; H5N6; Animal models; Germany.

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The #Emergence and Decennary #Distribution of Clade 2.3.4.4 #HPAI #H5Nx (Microorganisms., abstract)

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

Microorganisms. 2019 May 29;7(6). pii: E156. doi: 10.3390/microorganisms7060156.

The Emergence and Decennary Distribution of Clade 2.3.4.4 HPAI H5Nx.

Antigua KJC1, Choi WS2, Baek YH3, Song MS4.

Author information: 1 College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. tineantigua@gmail.com. 2 College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. tuckgirlee@naver.com. 3 College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. microuni@chungbuk.ac.kr. 4 College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Korea. songminsuk@chungbuk.ac.kr.

 

Abstract

Reassortment events among influenza viruses occur naturally and may lead to the development of new and different subtypes which often ignite the possibility of an influenza outbreak. Between 2008 and 2010, highly pathogenic avian influenza (HPAI) H5 of the N1 subtype from the A/goose/Guangdong/1/96-like (Gs/GD) lineage generated novel reassortants by introducing other neuraminidase (NA) subtypes reported to cause most outbreaks in poultry. With the extensive divergence of the H5 hemagglutinin (HA) sequences of documented viruses, the WHO/FAO/OIE H5 Evolutionary Working Group clustered these viruses into a systematic and unified nomenclature of clade 2.3.4.4 currently known as “H5Nx” viruses. The rapid emergence and circulation of these viruses, namely, H5N2, H5N3, H5N5, H5N6, H5N8, and the regenerated H5N1, are of great concern based on their pandemic potential. Knowing the evolution and emergence of these novel reassortants helps to better understand their complex nature. The eruption of reports of each H5Nx reassortant through time demonstrates that it could persist beyond its usual seasonal activity, intensifying the possibility of these emerging viruses’ pandemic potential. This review paper provides an overview of the emergence of each novel HPAI H5Nx virus as well as its current epidemiological distribution.

KEYWORDS: H5Nx; avian; avian influenza; dissemination; epidemiology; evolution

PMID: 31146461 DOI: 10.3390/microorganisms7060156

Keywords: Avian Influenza; Reassortant strain; H5N1; H5N2; H5N3; H5N5; H5N6; H5N8; Poultry; Wild birds.

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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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#Microevolution and independent incursions as main forces shaping #H5 #Hemagglutinin diversity during a #H5N8 / #H5N5 highly pathogenic #avian #influenza #outbreak in #Czech Republic in 2017 (Arch Virol., abstract)

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

Arch Virol. 2018 Aug;163(8):2219-2224. doi: 10.1007/s00705-018-3833-7. Epub 2018 Apr 5.

Microevolution and independent incursions as main forces shaping H5 Hemagglutinin diversity during a H5N8/H5N5 highly pathogenic avian influenza outbreak in Czech Republic in 2017.

Nagy A1, Dán Á2, Černíková L3, Vitásková E3, Křivda V3, Horníčková J3, Masopust R3, Sedlák K3.

Author information: 1 State Veterinary Institute Prague, Sídlištní 136/24, 16503, Prague, Czech Republic. alexander.nagy@svupraha.cz. 2 National Food Chain Safety Office, Veterinary Diagnostic Institute, Tábornok utca 2, Budapest, 1143, Hungary. 3 State Veterinary Institute Prague, Sídlištní 136/24, 16503, Prague, Czech Republic.

 

Abstract

Here, we present a comprehensive analysis of the H5N8/H5N5 highly pathogenic avian influenza (HPAI) virus strains detected in the Czech Republic during an outbreak in 2017. Network analysis of the H5 Hemagglutinin (HA) from 99% of the outbreak localities suggested that the diversity of the Czech H5N8/H5N5 viruses was influenced by two basic forces: local microevolution and independent incursions. The geographical occurrence of the central node H5 HA sequences revealed three eco-regions, which apparently played an important role in the origin and further spread of the local H5N8/HPAI variants across the country. A plausible explanation for the observed pattern of diversity is also provided.

PMID: 29623433 DOI: 10.1007/s00705-018-3833-7 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N5; H5N8; Reassortant Strain; Poultry; Wild Birds; Czech Republic.

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#Phylogenetic and molecular #analysis of highly pathogenic #avian #influenza #H5N8 and #H5N5 viruses detected in #Poland in 2016-2017 (Tranbsound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2018 Jun 19. doi: 10.1111/tbed.12924. [Epub ahead of print]

Phylogenetic and molecular analysis of highly pathogenic avian influenza H5N8 and H5N5 viruses detected in Poland in 2016-2017.

Świętoń E1, Śmietanka K1.

Author information: 1 Department of Poultry Diseases, National Veterinary Research Institute, Pulawy, Poland.

 

Abstract

Sixty-five poultry outbreaks and sixty-eight events in wild birds were reported during the highly pathogenic H5N8/H5N5 avian influenza epidemic in Poland in 2016-2017. The analysis of all gene segment sequences of selected strains revealed cocirculation of at least four different genome configurations (genotypes) generated through reassortment of clade 2.3.4.4 H5N8 viruses detected in Russia and China in mid-2016. The geographical and temporal distribution of three H5N8 genotypes indicates separate introductions. Additionally, an H5N5 virus with a different gene configuration was detected in wild birds. The compilation of the results with those from studies on the virus’ diversity in Germany, Italy and the Netherlands revealed that Europe was affected by at least eight different H5N8/H5N5 reassortants. Analysis of the HA gene sequence of a larger subset of samples showed its diversification corresponding to the genotype classification. The close relationship between poultry and wild bird strains from the same locations observed in several cases points to wild birds as the primary source of the outbreaks in poultry.

KEYWORDS: highly pathogenic avian influenza; reassortment

PMID: 29920971 DOI: 10.1111/tbed.12924

Keywords: Avian Influenza; H5N8; H5N5; Reassortant Strain; Poultry; Wild Birds; Poland.

——

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 (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

Keywords: Avian Influenza; H5N1; H5N2; H5N5; H5N6; H5N8; Reassortant Strain.

——

#PB2 and #HA #mutations increase the virulence of highly pathogenic #H5N5 clade 2.3.4.4 #avian #influenza virus in mice (Arch Virol., abstract)

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

Arch Virol. 2018 Feb;163(2):401-410. doi: 10.1007/s00705-017-3631-7. Epub 2017 Oct 31.

PB2 and HA mutations increase the virulence of highly pathogenic H5N5 clade 2.3.4.4 avian influenza virus in mice.

Yu Z1, Cheng K2, Sun W3, Zhang X3, Xia X4,5,6, Gao Y7,8,9.

Author information: 1 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China. zhijun0215@gmail.com. 2 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 3 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China. 4 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China. xiaxzh@cae.cn. 5 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. xiaxzh@cae.cn. 6 The Military Veterinary Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi st, Changchun, 130122, People’s Republic of China. xiaxzh@cae.cn. 7 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China. gaoyuwei@gmail.com. 8 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. gaoyuwei@gmail.com. 9 The Military Veterinary Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi st, Changchun, 130122, People’s Republic of China. gaoyuwei@gmail.com.

 

Abstract

H5 clade 2.3.4.4 influenza A viruses pose a potential threat to public health and are a cause of public concern. Here, we generated mouse-adapted viruses of a waterfowl-origin H5N5 virus (H5 clade 2.3.4.4) to identify adaptive changes that confer increased virulence in mammals. After two passages, we obtained a mouse-adapted H5N5 virus that contained single amino acid substitutions in the PB2 (E627K) and hemagglutinin (HA) (F430L) proteins. We then analyzed the impact of these individual amino acid substitutions on viral pathogenicity to mammals. The 50% mouse lethal dose (MLD50) of the H5N5 virus containing the PB2-E627K substitution or the HA-F430L substitution was reduced 1000-fold or 3.16-fold, respectively. Furthermore, we found that PB2-E627K enhanced viral replication kinetics in vitro and in vivo. These results suggest that the PB2-E627K and HA-F430L substitutions are important for adaptation of H5N5 AIVs to mammals. These findings emphasize the importance of continued surveillance of poultry for H5N5 AIVs with these amino acid substitutions.

PMID: 29090366 DOI: 10.1007/s00705-017-3631-7 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N5; Reassortant Strain; Animal Models.

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