#H5N8 and #H7N9 packaging signals constrain #HA #reassortment with a seasonal #H3N2 #influenza A virus (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus

Maria C. White, Hui Tao, John Steel, and Anice C. Lowen

PNAS published ahead of print February 13, 2019 / DOI: https://doi.org/10.1073/pnas.1818494116

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved January 17, 2019 (received for review October 26, 2018)



Influenza A viruses (IAV) can exchange genetic material in coinfected cells in a process termed reassortment. The last three IAV pandemic strains arose from reassortment events involving human and nonhuman IAVs. Because introduction of the hemagglutinin (HA) gene from a nonhuman virus is required for a pandemic, we addressed the compatibility of human and avian IAV. We show that sequence differences between human and avian HA genes limit the potential for reassortment. However, human IAV still incorporated heterologous HA genes at a low level in coinfected animals. This observed low level of incorporation could become significant if reassortant viruses had a fitness advantage within the host, such as resistance to preexisting immunity, and highlights the continued need for IAV surveillance.



Influenza A virus (IAV) has a segmented genome, which (i) allows for exchange of gene segments in coinfected cells, termed reassortment, and (ii) necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Here, we evaluated the extent to which packaging signals prevent reassortment events that would raise concern for pandemic emergence. Specifically, we tested the compatibility of hemagglutinin (HA) packaging signals from H5N8 and H7N9 avian IAVs with a human seasonal H3N2 IAV. By evaluating reassortment outcomes, we demonstrate that HA segments carrying H5 or H7 packaging signals are significantly disfavored for incorporation into a human H3N2 virus in both cell culture and a guinea pig model. However, incorporation of the heterologous HAs was not excluded fully, and variants with heterologous HA packaging signals were detected at low levels in vivo, including in naïve contact animals. This work indicates that the likelihood of reassortment between human seasonal IAV and avian IAV is reduced by divergence in the RNA packaging signals of the HA segment. These findings offer important insight into the molecular mechanisms governing IAV emergence and inform efforts to estimate the risks posed by H7N9 and H5N8 subtype avian IAVs.

influenza A virus – reassortment – packaging – zoonosis – antigenic shift

Keywords: Influenza A; Pandemic Influenza; Seasonal Influenza; Avian Influenza; Reassortant strain; H3N2; H5N8; H7N9; Animal models.



#Review analysis and impact of co-circulating #H5N1 and #H9N2 #avian #influenza viruses in #Bangladesh (Epidemiol Infect., abstract)

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

Epidemiol Infect. 2018 Jul;146(10):1259-1266. doi: 10.1017/S0950268818001292. Epub 2018 May 21.

Review analysis and impact of co-circulating H5N1 and H9N2 avian influenza viruses in Bangladesh.

Parvin R1, Begum JA1, Nooruzzaman M1, Chowdhury EH1, Islam MR1, Vahlenkamp TW2.

Author information: 1 Department of Pathology,Faculty of Veterinary Science,Bangladesh Agricultural University,Mymensingh 2202,Bangladesh. 2 Faculty of Veterinary Medicine,Center of Infectious Diseases, Institute of Virology, University of Leipzig,An den Tierkliniken 29, 04103 Leipzig,Germany.



Almost the full range of 16 haemagglutinin (HA) and nine neuraminidase subtypes of avian influenza viruses (AIVs) has been detected either in waterfowl, land-based poultry or in the environment in Bangladesh. AIV infections in Bangladesh affected a wide range of host species of terrestrial poultry. The highly pathogenic avian influenza (AI) H5N1 and low pathogenic AI H9N2 were found to co-circulate and be well entrenched in the poultry population, which has caused serious damage to the poultry industry since 2007. By reviewing the available scientific literature, the overall situation of AIVs in Bangladesh is discussed. All Bangladeshi (BD) H5N1 and H9N2 AIV sequences available at GenBank were downloaded along with other representative sequences to analyse the genetic diversity among the circulating AIVs in Bangladesh and to compare with the global situation. Three different H5N1 clades, 2.2.2, and, have been detected in Bangladesh. Only is still present. The BD LP H9N2 viruses mostly belonged to the H9 G1 lineage but segregated into many branches, and some of these shared internal genes with HP viruses of subtypes H7N3 and H5N1. However, these reassortment events might have taken place before introduction to Bangladesh. Currently, H9N2 viruses continue to evolve their HA cleavage, receptor binding and glycosylation sites. Multiple mutations in the HA gene associated with adaptation to mammalian hosts were also observed. Strict biosecurity at farms and gradual phasing out of live-bird markets could be the key measures to better control AIVs, whereas stamping out is not a practicable option in Bangladesh. Vaccination also could be an additional tool, which however, requires careful planning. Continuous monitoring of AIVs through systematic surveillance and genetic characterisation of the viruses remains a hallmark of AI control.

KEYWORDS: Avian influenza; Bangladesh; H5N1; H9N2; co-circulation; genetic evolution

PMID: 29781424 DOI: 10.1017/S0950268818001292 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N1; H7N3; H9N2; Poultry; Wild Birds; Bangladesh.


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.


#Human-Origin #Influenza A(#H3N2) #Reassortant Viruses in #Swine, Southeast #Mexico (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 4—April 2019 / Research

Human-Origin Influenza A(H3N2) Reassortant Viruses in Swine, Southeast Mexico

Martha I. Nelson  , Carine Souza, Nídia S. Trovão, Andres Diaz, Ignacio Mena, Albert Rovira, Amy L. Vincent, Montserrat Torremorell, Douglas Marthaler1, and Marie R. Culhane

Author affiliations: National Institutes of Health, Bethesda, Maryland, USA (M.I. Nelson, N.S. Trovão); National Animal Disease Center, Ames, Iowa, USA (C. Souza, A.L. Vincent); Icahn School of Medicine at Mount Sinai, New York, New York, USA (N.S. Trovão, I. Mena); University of Minnesota, Saint Paul, Minnesota, USA (A. Diaz, A. Rovira, M. Torremorell, D. Marthaler, M.R. Culhane)



The genetic diversity of influenza A viruses circulating in swine in Mexico complicates control efforts in animals and presents a threat to humans, as shown by influenza A(H1N1)pdm09 virus. To describe evolution of swine influenza A viruses in Mexico and evaluate strains for vaccine development, we sequenced the genomes of 59 viruses and performed antigenic cartography on strains from 5 regions. We found that genetic and antigenic diversity were particularly high in southeast Mexico because of repeated introductions of viruses from humans and swine in other regions in Mexico. We identified novel reassortant H3N2 viruses with genome segments derived from 2 different viruses that were independently introduced from humans into swine: pandemic H1N1 viruses and seasonal H3N2 viruses. The Mexico swine viruses are antigenically distinct from US swine lineages. Protection against these viruses is unlikely to be afforded by US virus vaccines and would require development of new vaccines specifically targeting these diverse strains.

Keywords: Seasonal Influenza; Swine Influenza; Reassortant Strain; Pigs; Human; H1N1pdm09; H3N2; Mexico.


#Genetic and biological characterization of two #reassortant #H5N2 #avian #influenza A viruses isolated from #waterfowl in #China in 2016 (Vet Microbiol., abstract)

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

Vet Microbiol. 2018 Oct;224:8-16. doi: 10.1016/j.vetmic.2018.08.016. Epub 2018 Aug 15.

Genetic and biological characterization of two reassortant H5N2 avian influenza A viruses isolated from waterfowl in China in 2016.

Liu K1, Gao R1, Gu M2, Li J1, Shi L1, Sun W1, Liu D1, Gao Z1, Wang X2, Hu J2, Liu X2, Hu S2, Chen S2, Gao S2, Peng D2, Jiao XA2, Liu X3.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China. 2 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. 3 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. Electronic address: xfliu@yzu.edu.cn.



Two reassortant H5N2 viruses in which hemagglutinin (HA) was clustered into clade, were isolated from apparently healthy waterfowl in live poultry markets in Eastern China in 2016. We used specific pathogen-free chickens, mallard ducks, and BALB/c mice to evaluate the isolates’ biological characteristics in different animal models. The newly isolated reassortant H5N2 viruses were able to cause severe disease in chickens and effective contact transmission, only at high doses. Our pathogenicity studies in ducks yielded an interesting result: the intravenous pathogenicity index (IVPI) indicated that isolate A/goose/Eastern China/1106/2016(1106) was low pathogenic and the other isolate A/duck/Eastern China/YD1516/2016(YD1516) was of highly pathogenicity in ducks. However, our 50% duck lethal dose (DLD50) experiment demonstrated that these viruses were all of low pathogenicity (DLD50 > 107.0 EID50) in ducks. Additionally, despite the fact that reassortant H5N2 were of low pathogenicity in mice, they could bind to both avian-type (SAα-2,3 Gal) and human-type (SAα-2,6 Gal) receptors, suggesting that these isolates still present a high risk for human infection. Therefore, it is of great importance to implement continual surveillance of avian influenza virus (AIV) to protect both veterinary and public health.

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

KEYWORDS: Avian influenza virus; H5N2; Pathogenicity; Reassortant; Waterfowl

PMID: 30269795 DOI: 10.1016/j.vetmic.2018.08.016 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; Reassortant Strain; Wild birds; China.


#Reassortments Among #Avian #Influenza A(#H5N1) Viruses Circulating in #Indonesia, 2015–2016 (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 3—March 2019 / Research

Reassortments Among Avian Influenza A(H5N1) Viruses Circulating in Indonesia, 2015–2016

Desniwaty Karo-karo, Rogier Bodewes, Hendra Wibawa, Made Artika, Eko Sugeng Pribadi, D. Diyantoro, Widya Pratomo, Agus Sugama, Nani Hendrayani, Iin Indasari, Michael Haryadi Wibowo, David Handojo Muljono, Jan Arend Stegeman, Guus Koch  , and Diyantoro

Author affiliations: Utrecht University, Utrecht, the Netherlands (D. Karo-karo, R. Bodewes, J.A. Stegeman); Indonesian Ministry of Agriculture, Jakarta, Indonesia (D. Karo-karo, H. Wibawa); Bogor Agricultural University, Bogor, Indonesia (I.M. Artika, E.S. Pribadi, D, Diyantoro, W. Pratomo); Eijkman Institute for Molecular Biology, Jakarta (I.M. Artika, D.H. Muljono); Livestock and Animal Health Agency of District Subang, Subang, Indonesia (A. Sugama)



Highly pathogenic avian influenza (HPAI) A(H5N1) viruses have been circulating since 2003 in Indonesia, with major impacts on poultry health, severe economic losses, and 168 fatal laboratory-confirmed human cases. We performed phylogenetic analysis on 39 full-genome H5N1 virus samples collected during outbreaks among poultry in 2015–2016 in West Java and compared them with recently published sequences from Indonesia. Phylogenetic analysis revealed that the hemagglutinin gene of all samples belonged to 2 genetic groups in clade We also observed these groups for the neuraminidase, nucleoprotein, polymerase, and polymerase basic 1 genes. Matrix, nonstructural protein, and polymerase basic 2 genes of some HPAI were most closely related to clade 2.1.3 instead of clade, and, a polymerase basic 2 gene was most closely related to Eurasian low pathogenicity avian influenza. Our results detected a total of 13 reassortment types among HPAI in Indonesia, mostly in backyard chickens in Indramayu.

Keywords: Avian Influenza; H5N1; Reassortant Strain; Poultry; Indonesia.


Characterization of a novel #reassortant #H7N3 highly pathogenic #avian #influenza virus isolated from a #poultry #meat product taken on a passenger flight to #Japan (J Vet Med Sci., abstract)

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

J Vet Med Sci. 2019 Jan 24. doi: 10.1292/jvms.18-0628. [Epub ahead of print]

Characterization of a novel reassortant H7N3 highly pathogenic avian influenza virus isolated from a poultry meat product taken on a passenger flight to Japan.

Shibata A1, Harada R1, Okamatsu M2, Matsuno K2,3, Arita T4, Suzuki Y4, Shirakura M4, Odagiri T4, Takemae N5, Uchida Y5, Saito T5, Sakoda Y2,3, Osaka H1.

Author information: 1 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries. 2 Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University. 3 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University. 4 Influenza Virus Research Center, National Institute of Infectious Diseases. 5 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO).



A new reassortant H7N3 avian influenza virus (AIV) was isolated from a duck meat product that was illegally taken on board a passenger flight from China to Japan in March 2018. Sequencing analysis revealed that the H7N3 isolate, A/duck/Japan/AQ-HE30-1/2018 (Dk/HE30-1) (H7N3), was a reassortant highly pathogenic avian influenza virus (HPAIV) that contained the haemagglutinin (HA) gene of Chinese H7N9 HPAIV. Dk/HE30-1 (H7N3) possessed a novel polybasic sequence motif PEVPKRRRTAR/GLF at the HA cleavage site that has never previously been reported in H7 HPAIVs. The HA antigenicity of Dk/HE30-1 (H7N3) slightly differed from that of H7N9 HPAIVs previously reported. These findings will help further our knowledge of the circulation and genetic evolution of emerging AIVs in endemic areas.

KEYWORDS: H7N3 subtype; highly pathogenic avian influenza virus; reassortant virus

PMID: 30674734 DOI: 10.1292/jvms.18-0628

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Poultry; Japan; China.