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PloS one2015; 10(11); e0143094; doi: 10.1371/journal.pone.0143094

Pathology of Equine Influenza virus (H3N8) in Murine Model.

Abstract: Equine influenza viruses (EIV)-H3N8 continue to circulate in equine population throughout the world. They evolve by the process of antigenic drift that leads to substantial change in the antigenicity of the virus, thereby necessitating substitution of virus strain in the vaccines. This requires frequent testing of the new vaccines in the in vivo system; however, lack of an appropriate laboratory animal challenge model for testing protective efficacy of equine influenza vaccine candidates hinders the screening of new vaccines and other therapeutic approaches. In the present investigation, BALB/c mouse were explored for suitability for conducting pathogenecity studies for EIV. The BALB/c mice were inoculated intranasally @ 2×106.24 EID50 with EIV (H3N8) belonging to Clade 2 of Florida sublineage and monitored for setting up of infection and associated parameters. All mice inoculated with EIV exhibited clinical signs viz. loss in body weights, lethargy, dyspnea, etc, between 3 and 5 days which commensurate with lesions observed in the respiratory tract including rhinitis, tracheitis, bronchitis, bronchiolitis, alveolitis and diffuse interstitial pneumonia. Transmission electron microscopy, immunohistochemistry, virus quantification through titration and qRT-PCR demonstrated active viral infection in the upper and lower respiratory tract. Serology revealed rise in serum lactate dehydrogenase levels along with sero-conversion. The pattern of disease progression, pathological lesions and virus recovery from nasal washings and lungs in the present investigations in mice were comparable to natural and experimental EIV infection in equines. The findings establish BALB/c mice as small animal model for studying EIV (H3N8) infection and will have immense potential for dissecting viral pathogenesis, vaccine efficacy studies, preliminary screening of vaccine candidates and antiviral therapeutics against EIV.
Publication Date: 2015-11-20 PubMed ID: 26587990PubMed Central: PMC4654517DOI: 10.1371/journal.pone.0143094Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the use of BALB/c mice as a model for studying Equine Influenza Virus (H3N8) infection. Results suggest that BALB/c mice simulate natural and experimental EIV infection in equines effectively and could be used for testing new vaccines and other therapeutics.

Objectives and Rationale

  • The study aims to address the lack of an appropriate laboratory animal challenge model for testing protective efficacy of equine influenza vaccine candidates.
  • The research focuses on Equine Influenza Virus (EIV)-H3N8, which circulates in equine populations globally and evolves through antigenic drift, changing its antigenicity and resulting in the need for frequent vaccination strategy shifts.
  • The intent is to investigate and establish BALB/c mice as a suitable model for conducting experiments related to EIV, primarily due to their small size and ease of handling.

Methodology

  • BALB/c mice were inoculated intranasally with EIV (H3N8) belonging to Clade 2 of the Florida sublineage.
  • Inoculation was done at a concentration of 2×106.24 EID50 (a measurement of the virus’s potency in terms of its ability to induce infection).
  • The mice were then closely observed for clinical indicators such as weight loss, lethargy and difficulty in breathing, along with any changes in the appearance of the respiratory tract.
  • Virus quantification, serology, transmission electron microscopy and immunohistochemistry tests were used to confirm active viral infection in the upper and lower respiratory tract.

Findings

  • The research found that all mice inoculated with EIV exhibited clinical signs between 3 and 5 days, such as loss in body weight, lethargy, and difficulty breathing. This is typically seen with respiratory tract lesions including rhinitis, tracheitis, bronchitis, bronchiolitis, alveolitis and diffuse interstitial pneumonia.
  • The disease progression, pathological lesions and virus recovery from nasal washings and lung samples in the mice were found to be comparable to natural and experimental EIV infection in equines.
  • The study also recorded a rise in serum lactate dehydrogenase levels alongside sero-conversion, indicating a response to the virus.

Conclusion

  • The study successfully establishes BALB/c mice as an effective model for studying EIV (H3N8) infection.
  • The findings indicate potential for using this model for vaccine efficacy studies, preliminary screening of vaccine candidates and antiviral therapeutics against EIV.

Cite This Article

APA
Pavulraj S, Bera BC, Joshi A, Anand T, Virmani M, Vaid RK, Shanmugasundaram K, Gulati BR, Rajukumar K, Singh R, Misri J, Singh RK, Tripathi BN, Virmani N. (2015). Pathology of Equine Influenza virus (H3N8) in Murine Model. PLoS One, 10(11), e0143094. https://doi.org/10.1371/journal.pone.0143094

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 11
Pages: e0143094
PII: e0143094

Researcher Affiliations

Pavulraj, Selvaraj
  • National Research Centre on Equines, Hisar, Haryana, India.
Bera, Bidhan Chandra
  • National Research Centre on Equines, Hisar, Haryana, India.
Joshi, Alok
  • Veterinary Hospital-Naini, Barakot, Almora, Uttarakhand, India.
Anand, Taruna
  • National Research Centre on Equines, Hisar, Haryana, India.
Virmani, Meenakshi
  • Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary & Animal Sciences, Hisar, Haryana, India.
Vaid, Rajesh Kumar
  • National Research Centre on Equines, Hisar, Haryana, India.
Shanmugasundaram, Karuppusamy
  • National Research Centre on Equines, Hisar, Haryana, India.
Gulati, Baldev Raj
  • National Research Centre on Equines, Hisar, Haryana, India.
Rajukumar, K
  • National Institute of High Security Animal Diseases, Bhopal, MP, India.
Singh, Rajendra
  • Division of Pathology, Indian Veterinary Research Institute, Bareilly, UP, India.
Misri, Jyoti
  • Division of Animal Science, Krishi Bhavan, New Delhi, India.
Singh, Raj Kumar
  • Indian Veterinary Research Institute, Bareilly, UP, India.
Tripathi, Bhupendra Nath
  • National Research Centre on Equines, Hisar, Haryana, India.
Virmani, Nitin
  • National Research Centre on Equines, Hisar, Haryana, India.

MeSH Terms

  • Animals
  • Disease Models, Animal
  • Horse Diseases / pathology
  • Horse Diseases / virology
  • Horses / virology
  • Influenza A Virus, H3N8 Subtype / immunology
  • Influenza A Virus, H3N8 Subtype / pathogenicity
  • Mice
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 5 times.
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