Intra- and interhost evolutionary dynamics of equine influenza virus.
Abstract: Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from individual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic diversity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host.
Publication Date: 2010-05-05 PubMed ID: 20444896PubMed Central: PMC2898244DOI: 10.1128/JVI.00112-10Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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The research reveals the evolutionary dynamics of the equine influenza virus in horses, on both an intra- and interhost level, uncovering the potential changes in antigenicity and the possibility of virus strain reassortment, a key factor for cross-species transmission and immune evasion.
Detailed Explanation of Research
Aim of the Study
- The study aimed to investigate the evolutionary process of the equine influenza virus (EIV) within a single host (intra-host level) and how it changes when it is transmitted between different hosts (inter-host level).
Methodology
- The researchers focused particularly on the hemagglutinin 1 gene, a crucial factor affecting the host range and a main target of neutralizing antibodies.
- Clonal sequencing of the hemaglutinin 1 gene derived from individual animals at different times post-infection was performed to capture the evolutionary dynamics of EIV.
Findings
- It was found that even though the population consensus sequence (average genetic makeup of a viral population) remained constant, genetically distinct subpopulations of the virus persisted throughout the infection and were transmitted between hosts.
- Some of these virus variants were anticipated to alter antigenicity, changing how the immune system recognizes and responds to them.
- During their research, the team also found a natural case of mixed infection in a horse during an outbreak of equine influenza, suggesting the possibility of reassortment or mixing of different strains of the virus.
Implications
- The results suggest that the previously understood transmission bottlenecks—limits to how much the virus can change and still successfully infect a new host—may not be as narrow as formerly believed.
- The genetic diversity necessary for the virus to adapt to new host species may already partly exist in the donor host, and can potentially be transmitted to the recipient host.
- The study therefore provides valuable insights that could help track the evolution, cross-species transmission and potential emergence of new or more virulent strains of the equine influenza virus.
Cite This Article
APA
Murcia PR, Baillie GJ, Daly J, Elton D, Jervis C, Mumford JA, Newton R, Parrish CR, Hoelzer K, Dougan G, Parkhill J, Lennard N, Ormond D, Moule S, Whitwham A, McCauley JW, McKinley TJ, Holmes EC, Grenfell BT, Wood JL.
(2010).
Intra- and interhost evolutionary dynamics of equine influenza virus.
J Virol, 84(14), 6943-6954.
https://doi.org/10.1128/JVI.00112-10 Publication
Researcher Affiliations
- Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, CB3 0ES Cambridge, England, United Kingdom.
MeSH Terms
- Animals
- Disease Outbreaks / veterinary
- Dogs
- Evolution, Molecular
- Hemagglutinin Glycoproteins, Influenza Virus / classification
- Hemagglutinin Glycoproteins, Influenza Virus / genetics
- Hemagglutinin Glycoproteins, Influenza Virus / immunology
- Horse Diseases / epidemiology
- Horse Diseases / genetics
- Horse Diseases / transmission
- Horse Diseases / virology
- Horses
- Humans
- Immune Evasion
- Influenza A Virus, H3N8 Subtype / genetics
- Influenza A Virus, H3N8 Subtype / immunology
- Influenza A Virus, H3N8 Subtype / pathogenicity
- Influenza, Human / epidemiology
- Influenza, Human / genetics
- Influenza, Human / transmission
- Influenza, Human / virology
- Likelihood Functions
- Mutation
- Orthomyxoviridae Infections / epidemiology
- Orthomyxoviridae Infections / genetics
- Orthomyxoviridae Infections / transmission
- Orthomyxoviridae Infections / veterinary
- Orthomyxoviridae Infections / virology
- Phylogeny
Grant Funding
- R24 HD047879 / NICHD NIH HHS
- R01 GM083983 / NIGMS NIH HHS
- R01 GM083983-01 / NIGMS NIH HHS
- R01 GM080533 / NIGMS NIH HHS
- Wellcome Trust
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