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The Journal of general virology2024; 105(8); 002016; doi: 10.1099/jgv.0.002016

Genetic and antigenic characterization of two diarrhoeicdominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population.

Abstract: Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013-2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.
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Publication Date: 2024-08-20 PubMed ID: 39163114PubMed Central: PMC11335307DOI: 10.1099/jgv.0.002016Google 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.

Overview

  • This study investigates two major rotavirus A genotypes (G3P[12] and G14P[12]) causing diarrhea in foals worldwide, characterizing their genomes and antigenic differences to inform disease control and vaccine development.

Background

  • Equine rotavirus species A (ERVA) is a significant cause of diarrhea in young horses, leading to economic losses globally.
  • The two dominant ERVA genotypes involved are G3P[12] and G14P[12].
  • ERVA has zoonotic potential as it can generate novel reassortant viruses capable of infecting humans, as seen in outbreaks between 2013-2019 where equine-like rotavirus caused childhood gastroenteritis.
  • Research on ERVA is challenging because standard cell culture systems for human rotaviruses are ineffective for isolating ERVA strains.

Methodology

  • The researchers developed and used an engineered cell line with defective antiviral innate immunity, allowing efficient isolation of ERVA G3P[12] and G14P[12] strains from diarrheic foals.
  • Genomic sequencing was performed on isolated strains to analyze their gene segments.
  • Antigenic characterization was conducted to assess cross-neutralization between the two genotypes.
  • Structural modeling was employed to explore the genetic basis for antigenic differences between the strains.

Key Findings

  • Both G3P[12] and G14P[12] share nearly identical genotypic constellations except in two gene segments: VP7 and VP6.
  • Specifically, G3P[12] has VP7 genotype G3 and VP6 genotype I6, whereas G14P[12] has VP7 genotype G14 and VP6 genotype I2.
  • Cross-neutralization studies showed limited cross-protection; antibodies against one genotype did not strongly neutralize the other.
  • This antigenic distinction helps explain why foals born to mares vaccinated with inactivated G3P[12] rotavirus vaccines experienced outbreaks caused by G14P[12].
  • Structural modeling identified genetic variations responsible for the antigenic divergence between the two genotypes, providing insight at the molecular level.

Implications

  • The limited cross-protection suggests that current monovalent G3P[12]-based vaccines may not be sufficient to protect against emerging G14P[12] infections.
  • Using an engineered cell line to isolate ERVA offers a new tool for isolating and studying these viruses efficiently, overcoming previous research hurdles.
  • The genetic and antigenic information provided lays the groundwork for designing improved vaccines that target multiple genotypes and enhance protection.
  • Understanding the structure-function relationship of ERVA surface proteins advances knowledge of infection mechanisms and may inform strategies to prevent zoonotic reassortment events.

Conclusion

  • This study characterizes the genetic makeup and antigenic differences of two equine rotavirus genotypes causing foal diarrhea worldwide.
  • The findings highlight the need for polyvalent vaccines to tackle the diversity of circulating ERVA strains.
  • The research paves the way for future studies on ERVA infection biology, pathogenesis, and vaccine-induced immunity, aiming to reduce disease burden in equine populations and minimize zoonotic risk.

Cite This Article

APA
Uprety T, Soni S, Sreenivasan C, Hause BM, Naveed A, Ni S, Graves AJ, Morrow JK, Meade N, Mellits KH, Adam E, Kennedy MA, Wang D, Li F. (2024). Genetic and antigenic characterization of two diarrhoeicdominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population. J Gen Virol, 105(8), 002016. https://doi.org/10.1099/jgv.0.002016

Publication

The Journal of general virology
ISSN: 1465-2099
NlmUniqueID: 0077340
Country: England
Language: English
Volume: 105
Issue: 8
PII: 002016

Researcher Affiliations

Uprety, Tirth
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Soni, Shalini
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Sreenivasan, Chithra
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Hause, Ben M
  • Department of Veterinary and Biomedical Sciences, Animal Disease Research and Diagnostic Laboratory, South Dakota State University, Brookings, South Dakota, 57007, USA.
Naveed, Ahsan
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Ni, Shuisong
  • Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
Graves, Amy J
  • Equine Diagnostic Solutions, LLC, 1501 Bull Lea Rd, Suite 104, Lexington, Kentucky 40511, USA.
Morrow, Jennifer K
  • Equine Diagnostic Solutions, LLC, 1501 Bull Lea Rd, Suite 104, Lexington, Kentucky 40511, USA.
Meade, Nathan
  • Division of Microbiology, Brewing, and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington, UK.
Mellits, Kenneth H
  • Division of Microbiology, Brewing, and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington, UK.
Adam, Emma
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Kennedy, Michael A
  • Department of Veterinary and Biomedical Sciences, Animal Disease Research and Diagnostic Laboratory, South Dakota State University, Brookings, South Dakota, 57007, USA.
Wang, Dan
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.
Li, Feng
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA.

MeSH Terms

  • Animals
  • Horses
  • Rotavirus / genetics
  • Rotavirus / immunology
  • Rotavirus / isolation & purification
  • Rotavirus / classification
  • Rotavirus Infections / veterinary
  • Rotavirus Infections / virology
  • Rotavirus Infections / immunology
  • Genotype
  • Horse Diseases / virology
  • Horse Diseases / immunology
  • Diarrhea / virology
  • Diarrhea / veterinary
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Genome, Viral / genetics
  • Phylogeny
  • Cell Line

Conflict of Interest Statement

The authors have read the journal’s policy and have the following conflicts: Ben Hause is currently employed by Cambridge Technologies, a company that produces animal vaccines, and this project was in part supported by Zoetis Animal Health that produces animal products including vaccines. Amy J. Graves, and Jennifer K. Morrow are employed by Equine Diagnostic Solutions, LLC, a company that offers diagnostic solutions for Equine diseases. This does not alter the authors adherence to all the ASM Journal policies on sharing data and materials.

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