#Functional #neuraminidase #inhibitor #resistance motifs in #avian #influenza A(#H5Nx) viruses (Antiviral Res., abstract)

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

Antiviral Research | Available online 1 August 2020, 104886 | In Press, Journal Pre-proof | Research paper

Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses

Dagmara Bialy, Holly Shelton, The Pirbright Institute, Pirbright, United Kingdom

Received 24 March 2020, Revised 13 July 2020, Accepted 16 July 2020, Available online 1 August 2020.

DOI: https://doi.org/10.1016/j.antiviral.2020.104886

 

Highlights

  • A R292K residue change in NA reduces susceptibility to NA inhibitor drugs (NAIs) in H5N6 and H5N2 avian influenza viruses.
  • All four mutations (E119V, H274Y, R292K and N294S) reducing susceptibility to NAIs in H5N6 viruses also reduced viral NA activity.
  • Reduced susceptibility to NA inhibitors in H5N6 did not attenuate virus replication efficiency in chicken cells or eggs.
  • A reduction of the viral HA affinity for sialic acid was observed in H5N6 viruses with reduced NA activity.

 

Abstract

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Past influenza virus pandemics seeded by zoonotic infection by avian influenza viruses (AIV) as well as the increasing number of human infections with AIV have shown the importance of having information about resistance to NAIs by avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we showed that a R292K substitution in H5N6 and H5N2 viruses significantly reduced susceptibility to three licenced NAIs: oseltamivir, zanamivir and peramivir. In contrast the mutations E119V, H274Y and N294S had more variable effects with NAI susceptibility being drug- and strain-specific. We measured the replicative fitness of NAI resistant H5N6 viruses and found that they replicated to comparable or significantly higher titres in primary chicken cells and in embryonated hens’ eggs as compared to wild type – despite the NA activity of the viral neuraminidase proteins being reduced. The R292K and N294S drug resistant H5N6 viruses had single amino acid substitutions in their haemagglutinin (HA): Y98F and A189T, respectively (H3 numbering) which reduced receptor binding properties possibly balancing the reduced NA activity seen. Our results demonstrate that the H5Nx viruses can support drug resistance mutations that confer reduced susceptibility to licenced NAIs and that these H5N6 viruses did not show diminished replicative fitness in avian cell cultures. Our results support the requirement for on-going surveillance of these strains in bird populations to include motifs associated with human drug resistance.

Keywords: Avian Influenza; H5N2; H5N6; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir.

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Immune escape #adaptive #mutations in the #H7N9 #avian #influenza #hemagglutinin protein increase virus #replication #fitness and decrease #pandemic #potential (J Virol., abstract)

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

Immune escape adaptive mutations in the H7N9 avian influenza hemagglutinin protein increase virus replication fitness and decrease pandemic potential

Pengxiang Chang, Joshua E. Sealy, Jean-Remy Sadeyen, Sushant Bhat, Deimante Lukosaityte, Yipeng Sun, Munir Iqbal

DOI: 10.1128/JVI.00216-20

 

ABSTRACT

H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T), 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in the field isolates in 2019. To investigate the potential threat of the serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo. They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in HA protein might pose a reduced pandemic risk but remain a heightened threat for poultry.

 

IMPORTANCE

Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in the virus-specific antiserum give rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunised or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chick embryo as well as (ii) increased acid and thermal stability, but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing indicated mutations remain a significant risk to the poultry due to antigenic drift and improved fitness for poultry.

Copyright © 2020 Chang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Avian Influenza; H7N9; Poultry; Evolution.

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14-Deoxy-11,12-didehydroandrographolide inhibits apoptosis in #influenza A(#H5N1) virus-infected #human #lung epithelial #cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity (Antiviral Res., abstract)

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

Antiviral Research | Available online 20 July 2020, 104885 | In Press, Journal Pre-proof

14-Deoxy-11,12-didehydroandrographolide inhibits apoptosis in influenza A(H5N1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity

Wentao Cai a, Haimei Wen a, Qinyang Zhou a, Lei Wu a, Yong Chen a, Hongbo Zhou b, Meilin Jin b

a Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, 430062, China; b State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China

Received 6 March 2020, Revised 26 May 2020, Accepted 22 June 2020, Available online 20 July 2020.

DOI: https://doi.org/10.1016/j.antiviral.2020.104885

 

Highlights

  • DAP inhibits caspase-3 and caspase-9 activation induced by influenza A(H5N1) virus in vitro.
  • DAP reduces mitochondrial membrane potential loss and represses cytochrome crelease.
  • DAP exerts anti-apoptotic effect via the caspase-9-dependent intrinsic pathway.
  • Anti-H5N1 ability of DAP partly depends on the inhibition of caspase-9 activity.
  • We propose that DAP is a potential candidate of anti-influenza drug.

 

Abstract

Influenza A virus (IAV) infection represents a global health challenge. Excavating antiviral active components from traditional Chinese medicine (TCM) is a promising anti-IAV strategy. Our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (DAP), a major ingredient of a TCM herb called Andrographis paniculata, shows anti-IAV activity that is mainly effective against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), and A/PR/8/34 (H1N1) in vitro and in vivo. However, the underlying anti-IAV molecular mechanism of DAP needs further investigation. In the present work, we found that DAP can significantly inhibit the apoptosis of human lung epithelial (A549) cells infected with A/chicken/Hubei/327/2004 (H5N1). After DAP treatment, the protein expression levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all obviously downregulated. However, DAP had no inhibitory effect on caspase-8 activity and cleaved caspase-8 production. Meanwhile, the efficacy of DAP in reducing the apoptotic cells was lost after using the inhibitor of caspase-3 or caspase-9 but remained intact after the caspase-8 inhibitor treatment. Moreover, DAP efficiently attenuated the dissipation of mitochondrial membrane potential, suppressed cytochrome c release from the mitochondria to the cytosol, and decreased the protein expression ratio of Bax/Bcl-2 in the mitochondrial fraction. Furthermore, the silencing of caspase-9 reduced the yield of nucleoprotein (NP) and disabled the inhibitory ability of DAP in NP production in A549 cells. Overall results suggest that DAP exerts its antiviral effects by inhibiting H5N1-induced apoptosis on the caspase-9-dependent intrinsic/mitochondrial pathway, which may be one of the anti-H5N1 mechanisms of DAP.

© 2020 Elsevier B.V. All rights reserved.

Keywords: A/H5N1; Avian Influenza; Antivirals.

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Full-length #genome #sequences of the first #H9N2 #avian #influenza viruses isolated in the Northeast of #Algeria (Virol J., abstract)

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

Virol J. 2020 Jul 17;17(1):108. doi: 10.1186/s12985-020-01377-z.

Full-length genome sequences of the first H9N2 avian influenza viruses isolated in the Northeast of Algeria

Abdelheq Barberis 1 2, Amine Boudaoud 3, Angelina Gorrill 4, Josianne  Loupias 4, Abdeljelil Ghram 5, Jihene Lachheb 5, Nadir Alloui 3, Mariette F Ducatez 6

Affiliations: 1 Centre de Recherche en Biotechnologie, Nouvelle Ville Ali Mendjeli, El Khroub, Algeria. abdelheqbarberis5@gmail.com. 2 LESPA, Département vétérinaire, ISVSA, Université de Batna, Batna, Algeria. abdelheqbarberis5@gmail.com. 3 LESPA, Département vétérinaire, ISVSA, Université de Batna, Batna, Algeria. 4 IHAP, Université de Toulouse, INRAE, ENVT, 23 Chemin des Capelles, 31076, Toulouse cedex, France. 5 Laboratoire d’Epidémiologie et de Microbiologie Vétérinaire, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia. 6 IHAP, Université de Toulouse, INRAE, ENVT, 23 Chemin des Capelles, 31076, Toulouse cedex, France. mariette.ducatez@envt.fr.

PMID: 32680533 DOI: 10.1186/s12985-020-01377-z

 

Abstract

Background:

H9N2 avian influenza viruses (AIV) has a worldwide geographic distribution and affects poultry of different types of production. H9N2 AIV was first reported in the Northeast of Algeria in April 2017, following an outbreak associated with high mortality, in broiler flocks. In the present study, we report full-length genome sequences of AIV H9N2, and the detailed phylogeny and molecular genetic analyses.

Methods:

Ten AIV H9N2 strains, collected in broiler flocks, were amplified in 9-day-old embryonated specific pathogen free (SPF) chicken eggs. Their full-length genomes were successfully sequenced and phylogenetic and molecular characterizations were conducted.

Results:

Phylogenetic analysis showed that the isolates were monophyletic, grouped within the G-1 lineage and were very close to Moroccan and Algerian strains identified in 2016 and 2017, respectively. The low pathogenicity of the strains was confirmed by the sequence motif (335RSSR/GLF341) at the hemagglutinin (HA) cleavage site. An exclusive substitution (T197A) that had not been previously reported for H9N2 viruses; but, conserved in some pandemic H1N1 viruses, was observed. When compared to the G1-like H9N2 prototype, the studied strains showed one less glycosylation site in HA, but 2-3 additional ones in the stalk of the neuraminidase (NA). The HA protein harbored the substitution 234 L, suggesting binding preference to human-like receptors. The NA protein harbored S372A and R403W substitutions, previously detected in H9N2 from Asia and the Middle East, and especially in H2N2 and H3N2 strains that caused human pandemics. Different molecular markers associated with virulence and mammalian infections have been detected in the viral internal proteins. The matrix M2 protein possessed the S31N substitution associated with drug resistance. The non-structural 1 (NS1) protein showed the “GSEV” PDZ ligand (PL) C-terminal motif and no 80-84 deletion.

Conclusion:

Characterized Algerian AIV isolates showed mutations that suggest increased zoonotic potential. Additional studies in animal models are required to investigate the pathogenicity of these H9N2 AIV strains. Monitoring their evolution in both migratory and domestic birds is crucial to prevent transmission to humans. Implementation of adequate biosecurity measures that limit the introduction and the propagation of AIV H9N2 in Algerian poultry farm is crucial.

Keywords: Algeria; Avian influenza H9N2; Full-length genome sequencing; Molecular characterization; Phylogenetic analysis.

Keywords: H9N2; Avian Influenza; Poultry; Algeria.

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#Evolution and #Antigenic #Drift of #Influenza A (#H7N9) Viruses, #China, 2017–2019 (Emerg Infect Dis., abstract)

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

Volume 26, Number 8—August 2020 | Dispatch

Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019

Jiahao Zhang1, Hejia Ye1, Huanan Li1, Kaixiong Ma, Weihong Qiu, Yiqun Chen, Ziwen Qiu, Bo Li, Weixin Jia, Zhaoping Liang, Ming Liao  , and Wenbao Qi

Author affiliations: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China (J. Zhang, H. Li, K. Ma, Y. Chen, Z. Qiu, B. Li, W. Jia, M. Liao, W. Qi); National Avian Influenza Para-Reference Laboratory, Ministry of Agriculture and Rural Affairs of the People’s Republic of China, Guangzhou (J. Zhang, H. Li, W. Jia, M. Liao, W. Qi); Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs of the People’s Republic of China, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, National Development and Reform Commission, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Guangzhou South China Biological Medicine Co., Ltd, Guangzhou (H. Ye, W. Qiu, Z. Liang); Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou (W. Jia, M. Liao, W. Qi)

 

Abstract

After a sharp decrease of influenza A(H7N9) virus in China in 2018, highly pathogenic H7N9 viruses re-emerged in 2019. These H7N9 variants exhibited a new predominant subclade and had been cocirculating at a low level in eastern and northeastern China. Several immune escape mutations and antigenic drift were observed in H7N9 variants.

Keywords: Avian Influenza; H7N9; China.

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Adjuvanted #H5N1 #influenza #vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans (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.]

Adjuvanted H5N1 influenza vaccine enhances both cross-reactive memory B cell and strain-specific naive B cell responses in humans

Ali H. Ellebedy,  Raffael Nachbagauer, Katherine J. L. Jackson, Ya-Nan Dai, Julianna Han, Wafaa B. Alsoussi, Carl W. Davis, Daniel Stadlbauer, Nadine Rouphael, Veronika Chromikova, Megan McCausland, Cathy Y. Chang, Mario Cortese, Mary Bower, Chakravarthy Chennareddy, Aaron J. Schmitz, Veronika I. Zarnitsyna, Lilin Lai, Arvind Rajabhathor, Cheyann Kazemian, Rustom Antia, Mark J. Mulligan,  Andrew B. Ward,  Daved H. Fremont, Scott D. Boyd, Bali Pulendran, Florian Krammer, and Rafi Ahmed

PNAS first published July 13, 2020 https://doi.org/10.1073/pnas.1906613117

Contributed by Rafi Ahmed, November 8, 2019 (sent for review April 19, 2019; reviewed by Robert L. Coffman and Marc K. Jenkins)

 

Significance

The development of a universal influenza vaccine is a major public health need globally, and identifying the optimal formulation will be an important first step for developing such a vaccine. Here we show that a two-dose immunization of humans with an inactivated, AS03-adjuvanted H5N1 avian influenza virus vaccine engaged both the preexisting memory and naive B cell compartments. Importantly, we show that the recruited memory B cells after first immunization were directed against conserved epitopes within the H5 HA stem region while the responses after the second immunization were mostly directed against strain-specific epitopes within the HA globular head. Taken together these findings have broad implications toward optimizing vaccination strategies for developing more effective vaccines against pandemic viruses.

 

Abstract

There is a need for improved influenza vaccines. In this study we compared the antibody responses in humans after vaccination with an AS03-adjuvanted versus nonadjuvanted H5N1 avian influenza virus inactivated vaccine. Healthy young adults received two doses of either formulation 3 wk apart. We found that AS03 significantly enhanced H5 hemagglutinin (HA)-specific plasmablast and antibody responses compared to the nonadjuvanted vaccine. Plasmablast response after the first immunization was exclusively directed to the conserved HA stem region and came from memory B cells. Monoclonal antibodies (mAbs) derived from these plasmablasts had high levels of somatic hypermutation (SHM) and recognized the HA stem region of multiple influenza virus subtypes. Second immunization induced a plasmablast response to the highly variable HA head region. mAbs derived from these plasmablasts exhibited minimal SHM (naive B cell origin) and largely recognized the HA head region of the immunizing H5N1 strain. Interestingly, the antibody response to H5 HA stem region was much lower after the second immunization, and this suppression was most likely due to blocking of these epitopes by stem-specific antibodies induced by the first immunization. Taken together, these findings show that an adjuvanted influenza vaccine can substantially increase antibody responses in humans by effectively recruiting preexisting memory B cells as well as naive B cells into the response. In addition, we show that high levels of preexisting antibody can have a negative effect on boosting. These findings have implications toward the development of a universal influenza vaccine.

 

Footnotes

1 Present address: Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.

2 Present address: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.

3 Present address: Departments of Pathology, and Microbiology & Immunology, Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305.

4 Present address: Division of Infectious Diseases and Immunology, Department of Medicine, New York University, New York, NY 10016.

5 To whom correspondence may be addressed. Email: rahmed@emory.edu.

Author contributions: A.H.E. and R. Ahmed designed research; A.H.E., R.N., Y.-N.D., J.H., W.B.A., D.S., N.R., V.C., M.M., C.Y.C., and C.K. performed research; K.J.L.J., M.C., M.B., C.C., A.J.S., L.L., A.R., M.J.M., A.B.W., D.H.F., S.D.B., B.P., and F.K. contributed new reagents/analytic tools; A.H.E., K.J.L.J., C.W.D., V.I.Z., R. Antia, D.H.F., and S.D.B. analyzed data; and A.H.E. and R. Ahmed wrote the paper.

Reviewers: R.L.C., University of California; and M.K.J., University of Minnesota.

The authors declare no competing interest.

Data deposition: Structures have been deposited in the Electron Microscopy Data Bank (accession codes: 1F03: EMD-20570 1H09: EMD-20571 1C01: EMD-20569) and BioProject Sequence Read Archive (accession no. PRJNA533650).

This article contains supporting information online  at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1906613117/-/DCSupplemental. Published under the PNAS license.

Keywords: Avian Influenza; H5N1; Vaccines.

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Development of a #monoclonal #antibody‐based antigen capture #ELISA for #detection of #H7N9 subtype #avian #influenza virus (J Med Virol., abstract)

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

Development of a monoclonal antibody‐based antigen capture enzyme‐linked immunosorbent assay for detection of H7N9 subtype avian influenza virus

Fan Yang,  Yixin Xiao,  Fumin Liu,  Hangping Yao,  Nanping Wu,  Haibo Wu

First published: 10 July 2020 | DOI:  https://doi.org/10.1002/jmv.26292

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26292

 

Abstract

In order to establish a rapid detection method for H7N9 avian influenza virus (AIV), monoclonal antibodies (mAbs) against hemagglutinin (HA) of H7N9 were developed to establish an antigen capture enzyme‐linked immunosorbent assay (AC‐ELISA). AC‐ELISA achieved high specificity and sensitivity, with a detection limit of 3.9 ng/ml for H7N9 HA protein (A/Zhejiang/DTID‐ZJU01/2013), and 2‐2 HA unit/100 μl for live H7N9 AIV. The inter‐ and intra‐assay coefficient of variation was less than 10%. Compared with conventional virus isolation detection, the sensitivity and specificity were 94.96% and 88.24%, respectively. AC‐ELISA proved to be a rapid and practical technique for detection of H7N9 AIV.

This article is protected by copyright. All rights reserved.

Keywords: Avian Influenza; H7N9; Monoclonal antibodies; Diagnostic tests.

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#H9N2 #influenza virus infections in #human #cells require a balance between #NA #sialidase activity and HA #receptor affinity (J Virol., abstract)

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

H9N2 influenza virus infections in human cells require a balance between NA sialidase activity and HA receptor affinity

Yasuha Arai, Emad Mohamed Elgendy, Tomo Daidoji, Madiha Salah Ibrahim, Takao Ono, Nongluk Sriwilaijaroen, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe

DOI: 10.1128/JVI.01210-20

 

ABSTRACT

Some avian influenza (AI) viruses have a deletion of up to 20-30 amino acids in their NA stalk. This has been associated with changes in virus replication and host range. Currently prevalent H9N2 AI viruses only have a 2 or 3 amino acid deletion, which were detected in G1 and Y280 lineage viruses, respectively. The effect of an NA deletion on the H9N2 phenotype has not been fully elucidated. In this study, we isolated G1 mutants that carried an 8 amino acid deletion in their NA stalk. To systematically analyze the effect of NA stalk length and concomitant (de)glycosylation on G1 replication and host range, we generated G1 viruses with various NA stalk lengths and were either glycosylated or not glycosylated. The stalk length was correlated with NA sialidase activity, using low molecular weight substrates, and with virus elution efficacy from erythrocytes. G1 virus replication in avian cells and eggs was positively correlated with NA stalk length, but was negatively correlated in human cells and mice. NA stalk length modulated G1 virus entry in host cells, with shorter stalks enabling more efficient G1 entry into human cells. However, with an HA with higher α2,6 Sia affinity, the effect of NA stalk length on G1 virus infection was reversed, with shorter NA stalks reducing virus entry into human cells. These results indicated that that a balance between HA binding affinity and NA sialidase activity, modulated by NA stalk length, was required for optimal G1 virus entry into human airway cells.

 

IMPORTANCE

H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage most prevalent worldwide. In this study, we isolated G1 variants carrying an 8 amino acid deletion in their NA stalk, which was, to our knowledge, the longest deletion found in H9N2 viruses in the field. NA stalk length was found to modulate G1 virus entry into host cells, with the effects being species-specific and dependent on the corresponding HA binding affinity. Our results suggested that, in nature, H9N2 G1 viruses balance their HA and NA functions by the NA stalk length, leading to the possible association of host range and virulence in poultry and mammals during the evolution of G1 lineage viruses.

Copyright © 2020 Arai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Avian Influenza; H9N2; Viral pathogenesis.

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#Epidemiology and #Genotypic #Diversity of #EA #Avian-Like #H1N1 #Swine #Influenza Viruses in #China (Virol Sin., abstract)

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

Epidemiology and Genotypic Diversity of Eurasian Avian-Like H1N1 Swine Influenza Viruses in China

Zhaomin Feng, Wenfei Zhu, Lei Yang, Jia Liu, Lijuan Zhou, Dayan Wang & Yuelong Shu

Virologica Sinica (2020)

 

Abstract

Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) outside European countries was first detected in Hong Kong Special Administrative Region (Hong Kong, SAR) of China in 2001. Afterwards, EA H1N1 SIVs have become predominant in pig population in this country. However, the epidemiology and genotypic diversity of EA H1N1 SIVs in China are still unknown. Here, we collected the EA H1N1 SIVs sequences from China between 2001 and 2018 and analyzed the epidemic and phylogenic features, and key molecular markers of these EA H1N1 SIVs. Our results showed that EA H1N1 SIVs distributed in nineteen provinces/municipalities of China. After a long-time evolution and transmission, EA H1N1 SIVs were continuously reassorted with other co-circulated influenza viruses, including 2009 pandemic H1N1 (A(H1N1)pdm09), and triple reassortment H1N2 (TR H1N2) influenza viruses, generated 11 genotypes. Genotype 3 and 5, both of which were the reassortments among EA H1N1, A(H1N1)pdm09 and TR H1N2 viruses with different origins of M genes, have become predominant in pig population. Furthermore, key molecular signatures were identified in EA H1N1 SIVs. Our study has drawn a genotypic diversity image of EA H1N1 viruses, and could help to evaluate the potential risk of EA H1N1 for pandemic preparedness and response.

Keywords: Avian Influenza; Swine Influenza; Influenza A; Reassortant strain; Pigs; H1N1; H1N2; H1N1pdm09; China.

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#Human #H9N2 #Avian #Influenza #Infection: #Epidemiological and #Clinical Characterization of 16 Cases in #China (Virol Sin., summary)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Human H9N2 Avian Influenza Infection: Epidemiological and Clinical Characterization of 16 Cases in China

Xuan Dong, Jiasong Xiong, Chaolin Huang, Jie Xiang, Wenjuan Wu, Nanshan Chen, Danning Wen, Chao Tu, Xueli Qiao, Liang Kang, Zhongzi Yao, Dingyu Zhang & Quanjiao Chen

Virologica Sinica (2020)

___

Dear Editor, The first human infections with avian influenza virus (AIV) H9N2 were  reported in 1998 (Guo et al. 1999). As of October 18th, 2019, 59 cases of human infection  with H9N2 have been reported globally, including 50 cases in China, three in Bangladesh,  four in Egypt, one in Pakistan and one in Oman (World Health  Organization. https://www.who.int/wer/en/; Peacock et al. 2019). Among the 59 patients,  three (5.1%) presented with severe pneumonia and 56 had mild influenza-like symptoms  (World Health Organization.  https://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/). In  general, human infections with H9N2 are sporadic and the majority of cases are mild  and non-fatal, and there is no evidence of human-to-human transmission to date  (Peacock et al. 2019).

(…)

Keywords: Avian Influenza; Human; H9N2; China.

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