#Equine #influenza virus in #Asia: phylogeographic pattern and molecular features revealed the circulation of an autochthonous lineage (J Virol., abstract)

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

Equine influenza virus in Asia: phylogeographic pattern and molecular features revealed the circulation of an autochthonous lineage

Samuel Miño, Laura Mojsiejczuk, Wei Guo, Haili Zhang, Ting Qi, Cheng Du, Xiang Zhang, Jingfei Wang, Rodolfo Campos, Xiaojun Wang

DOI: 10.1128/JVI.00116-19

 

ABSTRACT

Equine influenza virus (EIV) causes severe acute respiratory disease in horses. Currently, the strains belonging to the H3N8 genotype are divided into two clades, Florida clade 1 (FC1) and Florida clade 2 (FC2) which emerged in 2002. Both FC1and FC2 clades were reported in Asian and Middle East countries in the last decade. In this study, we described the evolution, epidemiology and molecular characteristic of the EIV lineages, with focus on those detected in Asia from 2007 to 2017. The full genome phylogeny showed that FC1 and FC2 constituted separated and divergent lineages, without evidence of reassortment between the clades. While FC1 evolved as a single lineage, the FC2 showed a divergent event around 2004 giving rise to two well supported and coexisting sub-lineages, European and Asian. Furthermore, two different spread patterns of EIV in Asian countries were identified. The FC1 outbreaks were caused by independent introductions of EIV from the Americas, being the Asian isolates genetically similar to the contemporary American lineages. On the other hand, the FC2 strains detected in Asian mainland countries conformed an autochthonous monophyletic group with a common ancestor dated in 2006 and showed evidence of an endemic circulation in local host. Characteristic aminoacidic signature patterns were detected in all viral proteins in both Asian-FC1 and FC2 populations. Several changes were located at the top of the HA1 protein, inside or near to antigenic sites. Further studies are needed to assess the potential impact of these antigenic changes in vaccination programs.

 

IMPORTANCE

The complex and continuous antigenic evolution of EIVs remains a major hurdle for vaccine development and the design of effective immunization programs. The present study provides a comprehensive analysis showing the EIV evolutionary dynamics, including the spread and circulation within the Asian continent and its relationship to global EIV populations over a 10-year period. Moreover, we provide a better understanding of EIV molecular evolution in Asian countries and its consequences on the antigenicity. The study underscores the association between the global horse movement and the circulation of EIV in this region. Understanding EIV evolution is imperative in order to mitigate the risk of outbreaks affecting horse industry and to help with the selection of the viral strains to be included in the formulation of future vaccines.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Equine Influenza; Horses; Asia Region.

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#Equine #Influenza Virus—A #Neglected, Reemergent Disease #Threat (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 6—June 2019 / Historical Review

Equine Influenza Virus—A Neglected, Reemergent Disease Threat

Alexandra Sack, Ann Cullinane, Ulziimaa Daramragchaa, Maitsetseg Chuluunbaatar, Battsetseg Gonchigoo, and Gregory C. Gray

Author affiliations: Institute of Veterinary Medicine, Ulaanbaatar, Mongolia (A. Sack, U. Daramragchaa, M. Chuluunbaatar, B. Gonchigoo); Duke University, Durham, North Carolina, USA (A. Sack, G.C. Gray); Irish Equine Centre, Johnstown, Ireland (A. Cullinane); Duke-NUS Medical School, Singapore, Singapore (G.C. Gray); Duke-Kunshan University, Kunshan, China (G.C. Gray)

 

Abstract

Equine influenza virus (EIV) is a common, highly contagious equid respiratory disease. Historically, EIV outbreaks have caused high levels of equine illness and economic damage. Outbreaks have occurred worldwide in the past decade. The risk for EIV infection is not limited to equids; dogs, cats, and humans are susceptible. In addition, equids are at risk from infection with avian influenza viruses, which can increase mortality rates. EIV is spread by direct and indirect contact, and recent epizootics also suggest wind-aided aerosol transmission. Increased international transport and commerce in horses, along with difficulties in controlling EIV with vaccination, could lead to emergent EIV strains and potential global spread. We review the history and epidemiology of EIV infections, describe neglected aspects of EIV surveillance, and discuss the potential for novel EIV strains to cause substantial disease burden and subsequent economic distress.

Keywords: Equine influenza; Horses; Influenza A.

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Absence of adaptive #evolution is the main #barrier against #influenza emergence in #horses in #Asia despite frequent virus interspecies transmission from #wildbirds (PLoS Pathog., abstract)

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

PLoS Pathog. 2019 Feb 7;15(2):e1007531. doi: 10.1371/journal.ppat.1007531. eCollection 2019 Feb.

Absence of adaptive evolution is the main barrier against influenza emergence in horses in Asia despite frequent virus interspecies transmission from wild birds.

Zhu H1, Damdinjav B2, Gonzalez G1, Patrono LV1,3, Ramirez-Mendoza H4, Amat JAR1, Crispell J1, Parr YA1, Hammond TA5, Shiilegdamba E6, Leung YHC7,8, Peiris M7, Marshall JF9, Hughes J1, Gilbert M6,10,11, Murcia PR1.

Author information: 1 MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. 2 State Central Veterinary Laboratory, Transboundary Animal Disease Laboratory, Avian Influenza Section, Ulaanbaatar, Mongolia. 3 Project Group Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany. 4 Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de Mexico, México. 5 Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, United Kingdom. 6 Wildlife Conservation Society, Bronx, NY, United States of America. 7 School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. 8 Laboratory Animal Unit, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. 9 Weipers Centre Equine Hospital, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom. 10 Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.  11 Department of Population Medicine and Diagnostic Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America.

 

Abstract

Virus ecology and evolution play a central role in disease emergence. However, their relative roles will vary depending on the viruses and ecosystems involved. We combined field studies, phylogenetics and experimental infections to document with unprecedented detail the stages that precede initial outbreaks during viral emergence in nature. Using serological surveys we showed that in the absence of large-scale outbreaks, horses in Mongolia are routinely exposed to and infected by avian influenza viruses (AIVs) circulating among wild birds. Some of those AIVs are genetically related to an avian-origin virus that caused an epizootic in horses in 1989. Experimental infections showed that most AIVs replicate in the equine respiratory tract without causing lesions, explaining the absence of outbreaks of disease. Our results show that AIVs infect horses but do not spread, or they infect and spread but do not cause disease. Thus, the failure of AIVs to evolve greater transmissibility and to cause disease in horses is in this case the main barrier preventing disease emergence.

PMID: 30731004 DOI: 10.1371/journal.ppat.1007531

Keywords: Avian Influenza; Equine Influenza; Horses; Wild Birds; Mongolia.

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#Mutation W222L at the receptor binding site of #hemagglutinin could facilitate viral adaption from #equine #influenza A(#H3N8) virus to #dogs (J Virol., abstract)

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

Mutation W222L at the receptor binding site of hemagglutinin could facilitate viral adaption from equine influenza A(H3N8) virus to dogs

Feng Wen a, Sherry Blackmon a, Alicia K. Olivier b, Lei Li c, Minhui Guan a, Hailiang Sun a, Peng George Wang c and Xiu-Feng Wan a*

Author Affiliations: a Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 USA; b Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 USA; c Department of Chemistry, Georgia State University, Atlanta, GA 30303 USA

 

ABSTRACT

An outbreak of respiratory disease caused by the equine-origin influenza A(H3N8) virus was first detected in dogs in 2004 and since then, has been enzootic among dogs. Currently, the molecular mechanisms underlying host adaption of this virus from horses to dogs is unknown. Here, we have applied quantitative binding, growth kinetics, and immunofluorescence analyses to elucidate these mechanisms. Our findings suggest that a substituation of W222L in the hemagglutinin of the equine-origin A(H3N8) virus facilitated its host adaption to dogs. This mutation increased binding avidity of the virus specifically to receptor glycans with N-glycolylneuraminic acid (Neu5Gc) and sialyl Lewis X (SLeX) motifs. We’ve demonstrated these motifs are abundantly located in the submucosal glands of dog trachea. Our findings also suggest that in addition to the type of glycosidic linkage (e.g., α 2,3-linkage or α2,6-linkage), the type of sialic acid (Neu5Gc or 5-N-acetyl neuraminic acid) and the glycan substructure (e.g., SLeX) also play an important role in host tropism of influenza A viruses.

 

Significance statement

Influenza A viruses (IAVs) cause a significant burden on human and animal health, and mechanisms for interspecies transmission of IAVs are far from being understood. Findings from this study suggest that an equine-origin A(H3N8) IAV with mutation W222L at its hemagglutinin increased binding to canine-specific receptors with sialyl Lewis X and Neu5Gc motifs and, thereby, may have facilitated viral adaption from horses to dogs. These findings suggest that in addition to the glycosidic linkage (e.g., α2,3-linked and α2,6-linked), the substructure in the receptor saccharides (e.g., sialyl Lewis X and Neu5Gc) could present an interspecies transmission barrier for IAVs and drive viral mutations to overcome such barriers.

 

FOOTNOTES

*Correspondence: Dr. Xiu-Feng Wan by wan@cvm.msstate.edu.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Equine Influenza; Canine Influenza; H3N8; Dogs.

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#Phylogenetic Analysis and Characterization of a Sporadic Isolate of #Equine #Influenza A #H3N8 from an Unvaccinated #Horse in 2015 (Viruses, abstract)

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

Viruses. 2018 Jan 11;10(1). pii: E31. doi: 10.3390/v10010031.

Phylogenetic Analysis and Characterization of a Sporadic Isolate of Equine Influenza A H3N8 from an Unvaccinated Horse in 2015.

Sreenivasan CC1, Jandhyala SS2, Luo S3, Hause BM4, Thomas M5, Knudsen DEB6, Leslie-Steen P7, Clement T8, Reedy SE9, Chambers TM10, Christopher-Hennings J11, Nelson E12, Wang D13,14, Kaushik RS15,16, Li F17,18,19.

Author information: 1 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. chithra.sreenivasan@sdstate.edu. 2 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. sunayana.shyamjandhyala@sdstate.edu. 3 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. sisi.luo@jacks.sdstate.edu. 4 Cambridge Technologies, Oxford Street Worthington, MN 56187, USA. bhause@cambridgetechnologies.com. 5 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. milton.thomas@sdstate.edu. 6 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. david.knudsen@sdstate.edu. 7 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. 8 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. travis.clement@sdstate.edu. 9 Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA. sereed0@uky.edu. 10 Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA. tmcham1@uky.edu. 11 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. jane.hennings@sdstate.edu. 12 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. eric.nelson@sdstate.edu. 13 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. dan.wang@sdstate.edu. 14 BioSNTR, Brookings, SD 57007, USA. dan.wang@sdstate.edu. 15 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. radhey.kaushik@sdstate.edu. 16 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. radhey.kaushik@sdstate.edu. 17 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA. feng.li@sdstate.edu. 18 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA. feng.li@sdstate.edu. 19 BioSNTR, Brookings, SD 57007, USA. feng.li@sdstate.edu.

 

Abstract

Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory disease affecting equid populations worldwide and has led to serious epidemics and transboundary pandemics. This study describes the phylogenetic characterization and replication kinetics of recently-isolated H3N8 virus from a nasal swab obtained from a sporadic case of natural infection in an unvaccinated horse from Montana, USA. The nasal swab tested positive for equine influenza by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Further, the whole genome sequencing of the virus confirmed that it was the H3N8 subtype and was designated as A/equine/Montana/9564-1/2015 (H3N8). A BLASTn search revealed that the polymerase basic protein 1 (PB1), polymerase acidic (PA), hemagglutinin (HA), nucleoprotein (NP), and matrix (M) segments of this H3N8 isolate shared the highest percentage identity to A/equine/Tennessee/29A/2014 (H3N8) and the polymerase basic protein 2 (PB2), neuraminidase (NA), and non-structural protein (NS) segments to A/equine/Malaysia/M201/2015 (H3N8). Phylogenetic characterization of individual gene segments, using currently available H3N8 viral genomes, of both equine and canine origin, further established that A/equine/Montana/9564-1/2015 belonged to the Florida Clade 1 viruses. Interestingly, replication kinetics of this H3N8 virus, using airway derived primary cells from multiple species, such as equine, swine, bovine, and human lung epithelial cells, demonstrated appreciable titers, when compared to Madin-Darby canine kidney epithelial cells. These findings indicate the broad host spectrum of this virus isolate and suggest the potential for cross-species transmissibility.

KEYWORDS: Florida Clade 1; equine influenza H3N8; hemagglutinin; horses; lineages

PMID: 29324680 DOI: 10.3390/v10010031

Keywords: Equine Influenza; Canine Influenza; Horses; USA; H3N8.

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#Mammalian #adaptation of an #avian #influenza A virus involves stepwise changes in NS1 (J Virol., abstract)

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

Mammalian adaptation of an avian influenza A virus involves stepwise changes in NS1

C. Chauché a, A. Nogales b, H. Zhu a, D. Goldfarb a, A.I. Ahmad Shanizza a, Q. Gu a, C.R Parrish c, L. Martínez-Sobrido b, J.F. Marshall d and P.R. Murcia a#

Author Affiliations: {a} MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. {b} Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA. {c} Baker Institute of Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, USA. {d} Equine Clinical Sciences Division, Weipers Centre Equine Hospital, School of Veterinary Medicine, University of Glasgow, United Kingdom

 

ABSTRACT

Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral non-structural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host-species barrier.

We characterised the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionary distinct NS1s counteract the IFN response using different and mutually exclusive mechanisms: while the NS1s of early EIVs block general gene expression by binding to the cellular polyadenylation specific factor 30 (CPSF30), NS1s from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and became rapidly selected during EIV evolution, highlighting the importance of evolutionary processes on immune evasion mechanisms during IAV adaptation. [150 words]

 

IMPORTANCE

Influenza A viruses (IAVs) infect certain avian reservoir species, and occasionally transfer to and cause epidemics of infections in some mammalian hosts. However, the processes by which IAVs gain the ability to efficiently infect and transmit in mammals remains unclear. H3N8 equine influenza virus (EIV) is an avian-origin virus that has successfully established a new lineage in horses in the early 1960, and is currently circulating worldwide in the equine population. Here we analysed the molecular evolution of the virulence factor non-structural protein 1 (NS1) and show that NS1s from different time periods after EIV emergence counteract the host innate immune response using contrasting strategies, which are associated with two mutations that appeared sequentially during EIV evolution. The results shown here indicate that the interplay between virus evolution and immune evasion plays a key role in IAV mammalian adaptation.

 

FOOTNOTES

# To whom correspondence should be addressed: Pablo Murcia, MRC – University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK, Pablo.Murcia@glasgow.ac.uk

Copyright © 2017 Chauché et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Influenza A; Equine Influenza; H3N8.

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#Aminoacid #substitution K186E in the #canine #influenza virus #H3N8 NS1 protein restores its ability to inhibit host gene expression (J Virol., abstract)

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

Amino acid substitution K186E in the canine influenza virus H3N8 NS1 protein restores its ability to inhibit host gene expression

Aitor Nogales a, Caroline Chauché b, Marta L. DeDiego a,c, David J. Topham a,c, Colin R. Parrish d, Pablo R. Murcia b and Luis Martínez-Sobrido a

uthor Affiliations: a Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA. b MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. c David Smith Center for Immunology and Vaccine Biology, University of Rochester, Rochester, New York, USA. d Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

 

ABSTRACT

Canine influenza viruses (CIVs) are the causative agents of canine influenza, a contagious respiratory disease in dogs, and include the equine-origin H3N8 and the avian-origin H3N2. Influenza A virus (IAV) non-structural protein 1 (NS1) is a virulence factor essential for counteracting the innate immune response. Here, we evaluated the ability of H3N8 CIV NS1 to inhibit host innate immune responses. We found that H3N8 CIV NS1 was able to efficiently counteract interferon (IFN) responses but was unable to block general gene expression in human or canine cells. Such ability was restored by a single amino acid substitution in position 186 (K186E) that resulted in NS1 binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a cellular protein involved in pre-mRNA processing. We also examined the frequency distribution of K186 and E186 among H3N8 CIVs and equine influenza viruses (EIVs), the ancestors of H3N8 CIV, and experimentally determined the impact of amino acid 186 in the ability of different CIV and EIV NS1s to inhibit general gene expression. In all cases, the presence of E186 was responsible for the control of host gene expression. Contrastingly, the NS1 protein of H3N2 CIV harbors E186 and blocks general gene expression in canine cells. Altogether, our results confirm previous studies on the strain-dependent ability of NS1 to block general gene expression. Moreover, the observed polymorphism on amino acid 186 between H3N8 and H3N2 CIVs might be the result of adaptive changes acquired during long-term circulation of avian-origin IAVs in mammals.

 

IMPORTANCE

Canine influenza is a respiratory disease of dogs caused by two CIV subtypes, the H3N8 and H3N2 viruses of equine and avian origin, respectively. Influenza NS1 is the main viral factor responsible for the control of host innate immune responses and changes in NS1 can play an important role in host adaptation. Here we assessed the ability of H3N8 CIV NS1 to inhibit host innate immune responses and gene expression. The H3N8 CIV NS1 did not block host gene expression but this activity was restored by a single amino acid substitution (K186E), which was responsible for NS1 binding to the host factor CPSF30. In contrast, the H3N2 CIV NS1, that contains E186, blocks general gene expression. Our results suggest that the ability to block host gene expression is not required for influenza replication in mammals but might be important in the long-term adaptation of avian-origin influenza viruses to mammals.

 

FOOTNOTES

To whom correspondence should be addressed: Luis Martínez-Sobrido, Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, Tel.: (585) 276-4733, e-mail: luis_martinez@urmc.rochester.edu

Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Keywords: Avian Influenza; Equine Influenza; Canine Influenza; H3N8; H3N2; Dogs.

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