Highly pathogenic #avian #influenza #H5N6 viruses exhibit enhanced #affinity for #human type #sialic acid #receptor and in-contact #transmission in model #ferrets (J Virol., abstract)

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

Highly pathogenic avian influenza H5N6 viruses exhibit enhanced affinity for human type sialic acid receptor and in-contact transmission in model ferrets

Honglei Sun a, Juan Pu a, YanDi Wei a, Yipeng Sun a, Jiao Hu b, Litao Liu a, Guanlong Xu a, Weihua Gao a, Chong Li a, Xuxiao Zhang a, Yinhua Huang a, Kin-Chow Chang c, Xiufan Liu b and Jinhua Liu a⇑

Author Affiliations: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China[a]; Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, China[b]; School of Veterinary Medicine and Science, University of Nottingham Sutton Bonington Campus, Sutton Bonington, UK[c]

 

ABSTRACT

Since May 2014, highly pathogenic avian influenza (HPAI) 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 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 in comparison with their 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 high affinity for human-type virus receptor. In comparison with 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.

FOOTNOTES: Correspondence and requests for materials should be addressed to J.L. (ljh@cau.edu.cn)

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; H5N6; Avian Influenza.

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The #molecular #characterizations of surface #proteins #hemagglutinin and #neuraminidase from recent #H5Nx #avian #influenza #viruses (J Virol., abstract)

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

The molecular characterizations of surface proteins hemagglutinin and neuraminidase from recent H5Nx avian influenza viruses

Hua Yang 1, Paul J. Carney 1, Vasiliy P. Mishin 1, Zhu Guo 1, Jessie C. Chang 1, David E. Wentworth 1, Larisa V. Gubareva 1 and James Stevens 1*

Author Affiliations: 1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329

 

ABSTRACT

During 2014, a subclade 2.3.4.4 HPAI A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015 the virus was detected in wild birds in Canada and the U.S. and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North America lineages. In particular, viruses were found with N1, N2 and N8 neuraminidase vRNAs, and are collectively referred to as H5Nx viruses. In the U. S., more than 48 million domestic birds have been affected. Here, we present a detailed structural and biochemical analysis of the surface antigens from H5N1, H5N2 and H5N8 in addition to a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses, and to continually assess future changes that may increase their pandemic potential.

 

IMPORTANCE

The H5Nx viruses emerging in North America, Europe, and Asia are of great public health concern. Herein, we report a molecular and structural study of the major surface proteins from several H5Nx influenza viruses. Our results improve the understanding of these new viruses and provide important information on their receptor preference and susceptibility to antivirals, which is central to pandemic risk assessment.

 

FOOTNOTES

*Corresponding author: James Stevens, PhD, Influenza Division, NCIRD, CCID, Centers for Disease Control and Prevention, 1600 Clifton Road – Mail Stop D-30, Atlanta, GA 30333, Phone: (404) 639-5008, Email: fwb4@cdc.gov

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; H5N1; H5N2; H5N6; H5N8; Avian Influenza.

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#Emergence and #dissemination of clade 2.3.4.4 #H5Nx #influenza viruses-how is the Asian HPAI H5 lineage maintained (Curr Opin Virol., abstract)

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

Curr Opin Virol. 2016 Mar 15;16:158-163. doi: 10.1016/j.coviro.2016.02.005. [Epub ahead of print]

Emergence and dissemination of clade 2.3.4.4 H5Nx influenza viruses-how is the Asian HPAI H5 lineage maintained.

Claes F1, Morzaria SP2, Donis RO3.

Author information: 1Food and Agriculture Organization of the United Nations (FAO), Regional Office for Asia and the Pacific, Bangkok, Thailand. Electronic address: Filip.Claes@fao.org. 2Food and Agriculture Organization of the United Nations (FAO), Viale delle Terme Di Caracalla, Rome 00153, Italy. 3Influenza Division, Centers for Disease Control and Prevention, USA. Electronic address: rdonis@cdc.gov.

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses containing the A/goose/Guangdong/96-like (GD/96) HA genes circulated in birds from four continents in the course of 2015 (Jan to Sept). A new HA clade, termed 2.3.4.4, emerged around 2010-2011 in China and revealed a novel propensity to reassort with NA subtypes other than N1, unlike dozens of earlier clades. Two subtypes, H5N6 and H5N8, have spread to countries in Asia (H5N6), Europe and North America (H5N8). Infections by clade 2.3.4.4 viruses are characterized by low virulence in poultry and some wild birds, contributing to wide geographical dissemination of the viruses via poultry trade and wild bird migration.

Copyright © 2016. Published by Elsevier B.V.

PMID: 26991931 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Avian Influenza; H5N1; H5N6; H5N8.

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#Detection of highly pathogenic #zoonotic #influenza #virus #H5N6 by RT-q #PCR (Virol J., abstract)

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

Virol J. 2015 Feb 8;12:18. doi: 10.1186/s12985-015-0250-3.

Detection of highly pathogenic zoonotic influenza virus H5N6 by reverse-transcriptase quantitative polymerase chain reaction. [      ]

Heine HG1, Foord AJ2, Wang J3, Valdeter S4, Walker S5, Morrissy C6, Wong FY7, Meehan B8.

Author information: 1CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Hans.Heine@csiro.au. 2CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Adam.Foord@csiro.au. 3CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Jianning.Wang@csiro.au. 4CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Stacey.Valdeter@csiro.au. 5CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Som.Walker@csiro.au. 6CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Chris.Morrissy@csiro.au. 7CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Frank.Wong@csiro.au. 8CSIRO Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC, 3220, Australia. Brian.Meehan@csiro.au.

 

Abstract

BACKGROUND:

Variant high pathogenicity avian influenza (HPAI) H5 viruses have recently emerged as a result of reassortment of the H5 haemagglutinin (HA) gene with different neuraminidase (NA) genes, including NA1, NA2, NA5, NA6 and NA8. These viruses form a newly proposed HA clade 2.3.4.4 (previously provisionally referred to as clade 2.3.4.6), and have been implicated in disease outbreaks in poultry in China, South Korea, Laos, Japan and Vietnam and a human fatality in China. There is real concern that this new clade may be wide spread and not readily identified using existing diagnostic algorithms.

FINDINGS:

Fluorescent probe based reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) assays were developed to facilitate the identification of novel clade 2.3.4.4 viruses of H5N6 subtype emerging in Asia. Assays were aimed at the haemagglutinin (HA) gene for clade identification and at the NA gene to identify N6. The HA assay employing a minor groove binder (MGB) probe was able to detect and differentiate A/duck/Laos/XBY004/2014(H5N6) and related influenza A(H5N6) virus isolates belonging to the proposed clade 2.3.4.4 from other H5 HPAI viruses. In addition, an Eurasian N6 assay was able to differentiate N6 from other NA subtypes.

CONCLUSIONS:

Laos influenza A(H5N6) virus representative of proposed clade 2.3.4.4, was detected and differentiated from viruses in other H5N1 clades using a clade-specific HA RT-qPCR assay whereas the N6-NA subtype was determined by an Eurasian N6 RT-qPCR assay. Such a clade-specific assay would be of particular value for surveillance and in diagnostic laboratories where sequencing is not readily available.

PMID: 25889293 [PubMed – indexed for MEDLINE]

PMCID: PMC4328077 / Free PMC Article

Keywords: Research; Abstracts; Avian Influenza; H5N6; Diagnostic Tests.

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