#Sporadic occurrence of #H9N2 #avian #influenza #infections in #human in #Anhui province, eastern #China: A notable #problem (Microb Pathog., abstract)

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

Microb Pathog. 2019 Dec 18:103940. doi: 10.1016/j.micpath.2019.103940. [Epub ahead of print]

Sporadic occurrence of H9N2 avian influenza infections in human in Anhui province, eastern China: A notable problem.

He J1, Wu Q2, Yu JL1, He L3, Sun Y1, Shi YL1, Chen QQ1, Ge YL1, Zhang ZH1, Li WW1, Hou S3, Zhu M3, Wu JB3, Su B1, Hu WB4, Pan HF5.

Author information: 1 Anhui Provincial Center for Disease Control and Prevention, 12560, Fanhua Avenue, Hefei, China; Key Laboratory for Medical and Health of the 13th Five-Year Plan, 12560, Fanhua Avenue, Hefei, Anhui, China. 2 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China. 3 Anhui Provincial Center for Disease Control and Prevention, 12560, Fanhua Avenue, Hefei, China. 4 School of Public Health and Social Work & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: w2.hu@qut.edu.au. 5 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China; School of Public Health and Social Work & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: panhaifeng1982@sina.com.

 

Abstract

H9N2 viruses can cause great economic losses to the domestic poultry industry when co-infected with other influenza viruses or pathogens. . To better understand the molecular characteristics of H9N2 avian influenza viruses (AIVs) and analyze the genetic evolutionary relationship, we isolated three H9N2 subtypes AIVs from nasopharyngeal swab specimens from the three cases reported in Anhui province since 2015, and systematically reviewed the genome-wide data of 21 poultry–isolated H9N2 viruses during 1998-2017. The six internal genes of three human-isolated viruses and recent poultry-isolated viruses (since 2014) in Anhui province presented high gene homologies with HPAI H7N9, even including H10N8 and H5N6. The three human-isolated H9N2 AIVs and poultry-isolated viruses (since 2008) in Anhui province were highly similar, and classified into genotype S. Seven N-linked potential glycosylation sites in the HA protein were detected in the three human-isolated viruses, which also appeared in poultry-isolated H9N2 AIVs. None of the human-isolated H9N2 AIVs had the I368V mutation in PB1 protein, but all the poultry-isolated H9N2 viruses in 2017 carried this mutation. Multidisciplinary, cross-regional and cross-sectoral approaches are warranted to address complex public health challenges and achieve the goal of ‘one health’.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: A (H9N2); Avian influenza; Avian influenza virus; Human infection; Poultry

PMID: 31863839 DOI: 10.1016/j.micpath.2019.103940

Keywords: Avian Influenza; H9N2; H5N6; H7N9; H10N8; Reassortant strain; Human; Poultry; China; Anhui.

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The #evolution and #genetic #diversity of #avian #influenza A(#H9N2) viruses in #Cambodia, 2015 – 2016 (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016

Annika Suttie, Songha Tok, Sokhoun Yann, Ponnarath Keo, Srey Viseth Horm, Merryn Roe, Matthew Kaye, San Sorn, Davun Holl, Sothyra Tum, Ian G. Barr, Aeron C. Hurt, Andrew R. Greenhill,  [ … ], Paul F. Horwood

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Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225428

 

Abstract

Low pathogenic A(H9N2) subtype avian influenza viruses (AIVs) were originally detected in Cambodian poultry in 2013, and now circulate endemically. We sequenced and characterised 64 A(H9N2) AIVs detected in Cambodian poultry (chickens and ducks) from January 2015 to May 2016. All A(H9) viruses collected in 2015 and 2016 belonged to a new BJ/94-like h9-4.2.5 sub-lineage that emerged in the region during or after 2013, and was distinct to previously detected Cambodian viruses. Overall, there was a reduction of genetic diversity of H9N2 since 2013, however two genotypes were detected in circulation, P and V, with extensive reassortment between the viruses. Phylogenetic analysis showed a close relationship between A(H9N2) AIVs detected in Cambodian and Vietnamese poultry, highlighting cross-border trade/movement of live, domestic poultry between the countries. Wild birds may also play a role in A(H9N2) transmission in the region. Some genes of the Cambodian isolates frequently clustered with zoonotic A(H7N9), A(H9N2) and A(H10N8) viruses, suggesting a common ecology. Molecular analysis showed 100% of viruses contained the hemagglutinin (HA) Q226L substitution, which favours mammalian receptor type binding. All viruses were susceptible to the neuraminidase inhibitor antivirals; however, 41% contained the matrix (M2) S31N substitution associated with resistance to adamantanes. Overall, Cambodian A(H9N2) viruses possessed factors known to increase zoonotic potential, and therefore their evolution should be continually monitored.

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Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016. PLoS ONE 14(12): e0225428. https://doi.org/10.1371/journal.pone.0225428

Editor: Charles J. Russell, St. Jude Children’s Research Hospital, UNITED STATES

Received: August 28, 2019; Accepted: November 4, 2019; Published: December 9, 2019

Copyright: © 2019 Suttie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This publication is the result of work conducted under a cooperative agreement with the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS), grant number IDSEP140020-01-00 (PH). The study was also funded, in part, by the US Agency for International Development (grant No. AID-442-G-14-00005) (PH). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health (IB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Avian Influenza; H9N2; H7N9; H9N2; H10N8; Reassortant strain; Cambodia; Antivirals; Drugs Resistance; Amantadine; Oseltamivir; Zanamivir.

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The #PB2 and M #genes are critical for the superiority of genotype S #H9N2 virus to genotype H in optimizing viral fitness of #H5Nx and #H7N9 #avian #influenza viruses in mice (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Oct 21. doi: 10.1111/tbed.13395. [Epub ahead of print]

The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice.

Hao X1,2,3, Hu J1,2,3, Wang X1,2,3, Gu M1,2,3, Wang J1,2,3, Liu D1,2,3, Gao Z1,2,3, Chen Y1,2,3, Gao R1,2,3, Li X1,2,3, Hu Z1,2,3, Hu S1,2,3, Liu X1,2,3, Peng D1,2,3, Jiao X2,3,4, Liu X1,2,3,4.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China. 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China. 3 Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. 4 Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.

 

Abstract

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, and contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1-like M and PB2 genes for the earlier F/98-like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1-like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared to the F/98-like counterpart, while the G1-like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1-like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: G1-like M and PB2; H5Nx; H7N9; avian influenza virus; viral fitness

PMID: 31631569 DOI: 10.1111/tbed.13395

Keywords: Avian Influenza; H5N1; H7N9; H10N8; H9N2; Reassortant strains.

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#Vaccination with viral #vectors expressing #NP, #M1 and chimeric #hemagglutinin induces broad protection against #influenza virus challenge in mice (Vaccine, abstract)

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

Vaccine. 2019 Aug 6. pii: S0264-410X(19)31016-3. doi: 10.1016/j.vaccine.2019.07.095. [Epub ahead of print]

Vaccination with viral vectors expressing NP, M1 and chimeric hemagglutinin induces broad protection against influenza virus challenge in mice.

Asthagiri Arunkumar G1, McMahon M2, Pavot V3, Aramouni M3, Ioannou A2, Lambe T3, Gilbert S4, Krammer F5.

Author information: 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA. 3 The Jenner Institute, University of Oxford, Oxford, UK. 4 The Jenner Institute, University of Oxford, Oxford, UK. Electronic address: sarah.gilbert@ndm.ox.ac.uk. 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: florian.krammer@mssm.edu.

 

Abstract

Seasonal influenza virus infections cause significant morbidity and mortality every year. Annual influenza virus vaccines are effective but only when well matched with circulating strains. Therefore, there is an urgent need for better vaccines that induce broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach to design such vaccines is based on targeting conserved regions of the influenza virus hemagglutinin. Sequential vaccination with chimeric hemagglutinin constructs can refocus antibody responses towards the conserved immunosubdominant stalk domain of the hemagglutinin, rather than the variable immunodominant head. A complementary approach for a universal influenza A virus vaccine is to induce T-cell responses to conserved internal influenza virus antigens. For this purpose, replication deficient recombinant viral vectors based on Chimpanzee Adenovirus Oxford 1 and Modified Vaccinia Ankara virus are used to express the viral nucleoprotein and the matrix protein 1. In this study, we combined these two strategies and evaluated the efficacy of viral vectors expressing both chimeric hemagglutinin and nucleoprotein plus matrix protein 1 in a mouse model against challenge with group 2 influenza viruses including H3N2, H7N9 and H10N8. We found that vectored vaccines expressing both sets of antigens provided enhanced protection against H3N2 virus challenge when compared to vaccination with viral vectors expressing only one set of antigens. Vaccine induced antibody responses against divergent group 2 hemagglutinins, nucleoprotein and matrix protein 1 as well as robust T-cell responses to the nucleoprotein and matrix protein 1 were detected. Of note, it was observed that while antibodies to the H3 stalk were already boosted to high levels after two vaccinations with chimeric hemagglutinins (cHAs), three exposures were required to induce strong reactivity across subtypes. Overall, these results show that a combinations of different universal influenza virus vaccine strategies can induce broad antibody and T-cell responses and can provide increased protection against influenza.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Influenza; M1; NP; Stalk; T-cell immunity; Universal influenza virus vaccine

PMID: 31399277 DOI: 10.1016/j.vaccine.2019.07.095

Keywords: Influenza A; H3N2; H7N9; H10N8; Vaccines; Animal models.

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The #PB2 and M genes of #genotype S #H9N2 virus contribute to the enhanced #fitness of #H5Nx and #H7N9 #avian #influenza viruses in chickens (Virology, abstract)

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

Virology. 2019 Jul 8;535:218-226. doi: 10.1016/j.virol.2019.07.001. [Epub ahead of print]

The PB2 and M genes of genotype S H9N2 virus contribute to the enhanced fitness of H5Nx and H7N9 avian influenza viruses in chickens.

Hao X1, Wang X1, Hu J1, Gu M1, Wang J1, Deng Y1, Jiang D1, He D1, Xu H1, Yang Y1, Hu Z1, Chen S1, Hu S1, Liu X1, Shang S1, Peng D1, Jiao X2, Liu X3.

Author information: 1 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; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. 2 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, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, 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, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Genotype S H9N2 viruses frequently donate their internal genes to facilitate the generation of novel influenza viruses, e.g., H5N6, H7N9, and H10N8, which have caused human infection. Genotype S was originated from the replacement of F/98-like M and PB2 genes of the genotype H with those from G1-like lineage. However, whether this gene substitution will influence the viral fitness of emerging influenza viruses remains unclear. We found that H5Nx and H7N9 viruses with G1-like PB2 or M gene exhibited higher virulence and replication than those with F/98-like PB2 or M in chickens. We also determined the functional significance of G1-like PB2 in conferring increased polymerase activity and improved nucleus transportation efficiency, and facilitated RNP nuclear export by G1-like M. Our results suggest that G1-like PB2 and M genes optimize viral fitness, and thus play a crucial role in the genesis of emerging influenza viruses that cause rising prevalence in chickens.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Avian influenza virus; Chickens; G1-like PB2 and M; H5Nx; H7N9; Viral fitness

PMID: 31325836  DOI: 10.1016/j.virol.2019.07.001

Keywords: Avian Influenza; H9N2; H5N6; H10N8; H7N9; Reassortant strain; Poultry.

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#mRNA #vaccines against #H10N8 and #H7N9 #influenza viruses of #pandemic #potential are immunogenic and well tolerated in healthy adults in phase 1 #RCTs (Vaccine, abstract)

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

Vaccine. 2019 May 9. pii: S0264-410X(19)30562-6. doi: 10.1016/j.vaccine.2019.04.074. [Epub ahead of print]

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

Feldman RA1, Fuhr R2, Smolenov I3, Mick Ribeiro A3, Panther L4, Watson M5, Senn JJ6, Smith M7, Almarsson Ӧ8, Pujar HS9, Laska ME3, Thompson J10, Zaks T11, Ciaramella G3.

Author information: 1 Miami Research Associates, 6280 Sunset Drive, Suite 600, So. Miami, FL 33143, USA. 2 PAREXEL International GmbH Klinikum Westend, House 18, Spandauer Damm 130, 14050 Berlin, Germany. Electronic address: Rainard.Fuhr@parexel.com. 3 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. 4 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Lori.Panther@modernatx.com. 5 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: mike.watson@modernatx.com. 6 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Joe.senn@modernatx.com. 7 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Mike.smith@modernatx.com. 8 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Orn.almarsson@modernatx.com. 9 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Hari.pujar@modernatx.com. 10 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: James.thompson@modernatx.com. 11 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Tal.zaks@modernatx.com.

 

Abstract

BACKGROUND:

We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.

METHODS:

Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64 years for H10N8 study; 18-49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay).

RESULTS:

H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study.

CONCLUSIONS:

The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses.

ClinicalTrials.gov NCT03076385 and NCT03345043.

Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

KEYWORDS: Immunogenicity; Pandemic influenza; Safety; Vaccines; mRNA

PMID: 31079849 DOI: 10.1016/j.vaccine.2019.04.074

Keywords: Avian Influenza; H7N9; H10N8; Vaccines.

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#Aerosol #exposure enhanced #infection of low pathogenic #avian #influenza viruses in #chickens (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Jan;66(1):435-444. doi: 10.1111/tbed.13039. Epub 2018 Nov 2.

Aerosol exposure enhanced infection of low pathogenic avian influenza viruses in chickens.

Jegede A1, Fu Q1, Lin M1,2, Kumar A2, Guan J1.

Author information: 1 Ottawa Laboratory (Fallowfield), Canadian Food Inspection Agency, Ottawa, Ontario, Canada. 2 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

 

Abstract

To assess the impact of different routes of inoculation on experimental infection of avian influenza (AI) viruses in chickens, this study compared virus replication and cytokine gene expression in respiratory and gastrointestinal organ tissues of chickens, which were inoculated with four low pathogenic subtypes, H6N1, H10N7, H10N8, and H13N6 AI viruses via the aerosol, intranasal, and oral routes respectively. Aerosol inoculation with the H6N1, H10N7, and H10N8 viruses significantly increased viral titres and upregulated the interferon (IFN)-γ, interleukin (IL)-6, and IL-1β genes in the trachea and lung tissues compared to intranasal or oral inoculation. Furthermore, one or two out of six chickens died following exposure to aerosolized H6N1 or H10N8 virus respectively. The H13N6 virus reached the lung via aerosol inoculation although failed to establish infection. Collectively, chickens were more susceptible to aerosolized AI viruses compared to intranasal or oral inoculation, and virus aerosols might post a significant threat to poultry health.

© 2018 Blackwell Verlag GmbH.

KEYWORDS: aerosols; and chickens; avian influenza viruses; cytokine gene expression; virus replication

PMID: 30307712 DOI: 10.1111/tbed.13039 [Indexed for MEDLINE]

Keywords: Avian Influenza; Animal models; Poultry; H6N1; H10N7; H10N8; H13N6.

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