A Novel #Neuraminidase-Dependent #Hemagglutinin #Cleavage Mechanism Enables the Systemic Spread of an #H7N6 #Avian #Influenza Virus (MBio, abstract)

[Source: MBio, full page: (LINK). Abstract, edited.]

A Novel Neuraminidase-Dependent Hemagglutinin Cleavage Mechanism Enables the Systemic Spread of an H7N6 Avian Influenza Virus

Hyeok-il Kwon, Young-Il Kim, Su-Jin Park, Eun-Ha Kim, Semi Kim, Young-Jae Si, Min-Suk Song, Philippe Noriel Q. Pascua, Elena A. Govorkova, Robert G. Webster, Richard J. Webby, Young Ki Choi

Kanta Subbarao, Editor

DOI: 10.1128/mBio.02369-19



In this study, we demonstrate a novel mechanism for hemagglutinin (HA) activation in a naturally occurring H7N6 avian influenza A virus strain, A/mallard duck/Korea/6L/2007 (A/Mdk/6L/07). This novel mechanism allows for systemic infection of chickens, ducks, and mice, and A/Mdk/6L/07 can replicate in vitro without exogenous trypsin and exhibits broad tissue tropism in animals despite the presence of a monobasic HA cleavage motif (PEIPKGR/G). The trypsin-independent growth phenotype requires the N6 neuraminidase and the specific recognition of glycine at the P2 position of the HA cleavage motif by a thrombin-like protease. Correspondingly, viral growth is significantly attenuated by the addition of a thrombin-like protease inhibitor (argatroban). These data provide evidence for a previously unrecognized virus replication mechanism and support the hypothesis that thrombin-mediated HA cleavage is an important virulence marker and potential therapeutic target for H7 influenza viruses.



The identification of virulence markers in influenza viruses underpins risk assessment programs and the development of novel therapeutics. The cleavage of the influenza virus HA is a required step in the viral life cycle, and phenotypic differences in viruses can be caused by changes in this process. Here, we describe a novel mechanism for HA cleavage in an H7N6 influenza virus isolated from a mallard duck. The mechanism requires the N6 protein and full activity of thrombin-like proteases and allows the virus to cause systemic infection in chickens, ducks, and mice. The thrombin-mediated cleavage of HA is thus a novel virulence determinant of avian influenza viruses.

Keywords: Avian Influenza; H7N6; Viral pathogenesis.


Low pathogenic #avian #influenza (#H7N6) virus causing an #outbreak in commercial Turkey #farms in #Chile (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2019;8(1):479-485. doi: 10.1080/22221751.2019.1595162.

Low pathogenic avian influenza (H7N6) virus causing an outbreak in commercial Turkey farms in Chile.

Jimenez-Bluhm P1, Bravo-Vasquez N2, Torchetti MK3, Killian ML3, Livingston B2, Herrera J4, Fuentes M4, Schultz-Cherry S2, Hamilton-West C1.

Author information: 1a Department of Preventive Veterinary Medicine, Faculty of Veterinary Sciences , Universidad de Chile , Santiago , Chile. 2b St. Jude Children’s Hospital , Memphis , TN , USA. 3c National Veterinary Services Laboratories , Ames , IA , USA. 4d Servicio Agrícola y Ganadero , Santiago , Chile.



In late 2016, an H7N6 low pathogenic avian influenza virus outbreak occurred in domestic turkeys in Central Chile. We characterized the genetic and antigenic properties of the outbreak virus and its experimental transmission in chickens. Our studies demonstrate that the outbreak virus is a reassortment of genes identified from Chilean wild bird viruses between 2013 and 2017 and displays molecular adaptations to poultry and antiviral resistance to adamantanes. Further, these wild bird viruses are also able to transmit in experimentally infected chickens highlighting the need for continued surveillance and improvement of biosecurity in poultry farms.

KEYWORDS: Chile; Influenza; South America; Turkey; avian influenza; poultry

PMID: 30924394 PMCID: PMC6456847 DOI: 10.1080/22221751.2019.1595162 Free PMC Article

Keywords: Avian Influenza; H7N6; Reassortant strain; Poultry; Chile.


Emergence of #waterfowl-originated #gene cassettes in HPAI #H7N9 viruses caused severe #human #infection in #Fujian, #China (Influenza Other Respir Viruses, abstract)

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

Influenza Other Respir Viruses. 2019 Jun 11. doi: 10.1111/irv.12657. [Epub ahead of print]

Emergence of waterfowl-originated gene cassettes in HPAI H7N9 viruses caused severe human infection in Fujian, China.

Yang L1, Xie J2,3, Zhang Y1, Zhu W1, Li X1, Wei H1, Li Z1, Zhao L2, Bo H1, Liu J1, Dong J1, Chen T1, Shu Y1,4, Weng Y2,3, Wang D1.

Author information: 1 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. 2 Fujian center for disease control and prevention, Fuzhou, China. 3 Fujian provincial key laboratory of zoonosis research, Fuzhou, China. 4 School of Public Health Shenzhen, Sun Yat-sen University, Guangdong, China.




Highly pathogenic avian influenza (HPAI) A(H7N9) virus emerged and caused human infections during the 2016-2017 epidemic wave of influenza A(H7N9) viruses in China. We report a human infection with HPAI H7N9 virus and six environmental isolates in Fujian Province, China.


Environmental surveillance was conducted in live poultry markets and poultry farms in Fujian, China. Clinical and epidemiologic data and samples were collected. Real-time RT-PCRs were conducted for each sample, and H7-positive samples were isolated using embryonated chicken eggs. Full genomes of the isolates were obtained by next-generation sequencing. Phylogenetic analysis and antigenic analysis were conducted.


A 59-year-old man who raised about 1000 ducks was identified as HPAI H7N9 infection. Six HPAI H7 viruses were isolated from environmental samples, including five H7N9 viruses and one H7N6 virus. Phylogenetic results showed the human and environmental viruses are highly genetically diverse and containing significantly different gene constellation from that of other HPAI H7N9 previously reported. The internal genes derived from H7N9/H9N2, H5N6, and the Eurasian wild-bird gene pool, indicating waterfowl-originated genotypes, have emerged in HPAI H7N9/N6 viruses and caused human infection.


The new genotypes raise the concern that these HPAI H7 viruses might transmit back into migratory birds and spread to other countries as the HPAI H5Nx viruses. Considering their capability of causing severe infections in both human and poultry, the HPAI H7 viruses in this study pose a risk to public health and the poultry industry and highlight the importance of sustained surveillance of these viruses.

© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

KEYWORDS: H7N9 virus; avian influenza; genetic diversity; infection

PMID: 31187583 DOI: 10.1111/irv.12657

Keywords: Avian Influenza; H5N6; H7N6; H7N9; H9N2; Reassortant Strain; Wild birds; Human; Fujian; China.


#H7N6 low pathogenic #avian #influenza #outbreak in commercial #turkey farms in #Chile caused by a native South American Lineage (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Apr 4. doi: 10.1111/tbed.13166. [Epub ahead of print]

H7N6 low pathogenic avian influenza outbreak in commercial turkey farms in Chile caused by a native South American Lineage.

Mathieu C1, Gonzalez A1, Garcia A1, Johow M1, Badia C1, Jara C1, Nuñez P1, Neira V2, Montiel NA3, Killian ML3, Brito BP4.

Author information: 1 Servicio Agrícola y Ganadero (SAG), Laboratorio y Estación Cuarentenaria de Lo Aguirre, Santiago, Chile. 2 Departamento de Medicina Preventiva, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, La Pintana, Santiago, Chile. 3 National Veterinary Services Laboratories, Science, Veterinary Services, Animal and Plant Health Inspection Service, U.S. Department of Agriculture, Ames, Iowa. 4 The ithree Institute, University of Technology Sydney, Sydney, New South Wales, Australia.



In December 2016, low pathogenic avian influenza (LPAI) caused by an H7N6 subtype was confirmed in a grow-out turkey farm located in Valparaiso Region, Chile. Depopulation of exposed animals, zoning, animal movement control and active surveillance were implemented to contain the outbreak. Two weeks later, a second grow-out turkey farm located 70 km north of the first site was also infected by H7N6 LPAI, which subsequently spilled over to one backyard poultry flock. The virus involved in the outbreak shared a close genetic relationship with Chilean aquatic birds’ viruses collected in previous years. The A/turkey/Chile/2017(H7N6) LPAI virus belonged to a native South American lineage. Based on the H7 and most of the internal genes’ phylogenies, these viruses were also closely related to the ones that caused a highly pathogenic avian influenza outbreak in Chile in 2002. Results from this study help to understand the regional dynamics of influenza outbreaks, highlighting the importance of local native viruses circulating in the natural reservoir hosts.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: Influenza in birds; Viruses; disease outbreaks; phylogeny; poultry

PMID: 30945819 DOI: 10.1111/tbed.13166

Keywords: Avian Influenza; H7N6; Poultry; Chile.


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.



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.


#Molecular characterization of a novel #reassortant #H7N6 subtype #avian #influenza virus from #poultry in Eastern #China, in 2016 (Arch Virol., abstract)

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

Arch Virol. 2017 Jan 19. doi: 10.1007/s00705-017-3219-2. [Epub ahead of print]

Molecular characterization of a novel reassortant H7N6 subtype avian influenza virus from poultry in Eastern China, in 2016.

Wu H1, Lu R2, Peng X1, Peng X1, Chen B1, Cheng L1, Wu N3.

Author information: 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. 2Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China. 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. flwnp2013@163.com.



During the surveillance for avian influenza viruses (AIVs) in live poultry markets in Eastern China, in 2016, a novel reassortant H7N6 AIV was isolated from a chicken. Phylogenetic analysis showed that this strain received its genes from H9N2, H7N9 and H5N6 AIVs infecting poultry in China. This strain showed moderate pathogenicity in mice and was able to replicate in mice without prior adaptation. Considering that this novel reassorted H7N6 virus was isolated from poultry in this study, it is possible that chickens play an important role in the generation of novel reassorted H7N6 AIVs.

KEYWORDS: Avian influenza viruses; Chickens; H7N6; Reassortment

PMID: 28105530 DOI: 10.1007/s00705-017-3219-2

[PubMed – as supplied by publisher]

Keywords: Avian Influenza; H7N6; H7N9; H9N2; Reassortant Strain; Poultry; China.


#Evolutionary #trajectories of two distinct #avian #influenza #epidemics: Parallelisms and divergences (Infect Genet Evol., abstract)

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

Infect Genet Evol. 2015 Aug;34:457-66. doi: 10.1016/j.meegid.2015.05.020. Epub 2015 May 20.

Evolutionary trajectories of two distinct avian influenza epidemics: Parallelisms and divergences.

Fusaro A1, Tassoni L2, Hughes J3, Milani A2, Salviato A2, Schivo A2, Murcia PR3, Bonfanti L2, Cattoli G2, Monne I2.

Author information: 1Istituto Zooprofilattico Sperimentale delle Venezie, viale dell’Università, 10, Legnaro (PD), Italy. Electronic address: afusaro@izsvenezie.it. 2Istituto Zooprofilattico Sperimentale delle Venezie, viale dell’Università, 10, Legnaro (PD), Italy. 3MRC-University of Glasgow Center for Virus Research, 464 Bearsden Road, Glasgow, United Kingdom.



Influenza A virus can quickly acquire genetic mutations that may be associated with increased virulence, host switching or antigenic changes. To provide new insights into the evolutionary dynamics and the adaptive strategies of distinct avian influenza lineages in response to environmental and host factors, we compared two distinct avian influenza epidemics caused by the H7N1 and H7N3 subtypes that circulated under similar epidemiological conditions, including the same domestic species reared in the same densely populated poultry area for similar periods of time. The two strains appear to have experienced largely divergent evolution: the H7N1 viruses evolved into a highly pathogenic form, while the H7N3 did not. However, a more detailed molecular and evolutionary analysis revealed several common features: (i) the independent acquisition of 32 identical mutations throughout the entire genome; (ii) the evolution and persistence of two sole genetic groups with similar genetic characteristics; (iii) a comparable pattern of amino acid variability of the HA proteins during the low pathogenic epidemics; and (iv) similar rates of nucleotide substitutions. These findings suggest that the evolutionary trajectories of viruses with the same virulence level circulating in analogous epidemiological conditions may be similar. In addition, our deep sequencing analysis of 15 samples revealed that 17 of the 32 parallel mutations were already present at the beginning of the two epidemics, suggesting that fixation of these mutations may occur with different mechanisms, which may depend on the fitness gain provided by each mutation. This highlighted the difficulties in predicting the acquisition of mutations that can be correlated to viral adaptation to specific epidemiological conditions or to changes in virus virulence.

Copyright © 2015 Elsevier B.V. All rights reserved.

KEYWORDS: Avian influenza virus; Deep sequencing; Evolutionary dynamics; H7 subtype; Molecular analysis; Parallel evolution

PMID: 26003682 [PubMed – indexed for MEDLINE]

Keywords: Research; Abstracts; Avian Influenza; H7N1; H7N3; Poultry.