Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 6

Comparative clinical, virological and pathological characterization of equine rotavirus A G3P[12] and G14P[12] infection in neonatal mice Open Access

Abstract

Group A rotavirus (RVA) infections are a leading cause of neonatal diarrhoea in foals. Neonatal mice could serve as a useful tool to study the pathogenesis of equine RVA (ERVA) as well as a preclinical model for assessment of vaccine efficacy. This study aimed to comparatively evaluate the clinical, virological and pathological features of ERVA G3P[12] and G14P[12] infection in neonatal mice and compare them with porcine OSU G5P[7] and bovine UK G6P[5] RVA reference strains. Neonatal mice orally inoculated with equine, bovine and porcine RVA developed short-lived diarrhoea at variable rates, G14P[12] (61%) and G3P[12] (88%). Viral replication kinetics for all strains were characterized by a gradual decline in viral load to levels below the limit of detection by 72–96 h post-infection (hpi), in line with the reduction in the number of infected enterocytes demonstrated via RNAscope hybridization. Importantly, the clinical and viral replication kinetics correlated with significant microscopic intestinal alterations characterized by enterocyte vacuolation, scalloping and hyperplasia with a peak occurring at 48 hpi and persisting until at least 96 hpi. Overall, neonatal mice develop a disease phenotype of short duration following infection with equine, porcine and bovine RVA strains characterized by diarrhoea and pronounced histological alterations in the intestinal villi. The limited intestinal viral replication is likely associated with host restriction. The clinical and pathological phenotypes developed by neonatal mice following experimental infection could serve as a preclinical tool to assess vaccine efficacy and for pathogenesis studies involving RVA of equine, porcine and bovine origin.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): bovine rotavirus A , equine rotavirus A , G14P[12] , G3P[12] , neonatal mice , porcine rotavirus A , rotavirus A and rotavirus tropism
Funding
This study was supported by the:
  • School of Veterinary Medicine, Louisiana State University (Award PG009641)
    • Principal Award Recipient: MarianoCarossino
  • National Institute of Food and Agriculture (Award 1433 Formula Funds)
    • Principal Award Recipient: MarianoCarossino
  • Grayson-Jockey Club Research Foundation (Award 863)
    • Principal Award Recipient: MarianoCarossino
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.002110
2025-06-05
2026-04-14

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/jgv/106/6/jgv002110.html?itemId=/content/journal/jgv/10.1099/jgv.0.002110&mimeType=html&fmt=ahah

References

  1. Matthijnssens J, Attoui H, Bányai K, Brussaard CPD, Danthi P et al. ICTV virus taxonomy profile: Sedoreoviridae 2022. J Gen Virol 2022; 103:10 [View Article]
     [Google Scholar]
  2. Matthijnssens J, Ciarlet M, Heiman E, Arijs I, Delbeke T et al. Full genome-based classification of rotaviruses reveals a common origin between human Wa-Like and porcine rotavirus strains and human DS-1-like and bovine rotavirus strains. J Virol 2008; 82:3204–3219 [View Article] [PubMed]
     [Google Scholar]
  3. Du Y, Chen C, Zhang X, Yan D, Jiang D et al. Global burden and trends of rotavirus infection-associated deaths from 1990 to 2019: an observational trend study. Virol J 2022; 19:166 [View Article] [PubMed]
     [Google Scholar]
  4. Bennett A, Bar-Zeev N, Cunliffe NA. Measuring indirect effects of rotavirus vaccine in low income countries. Vaccine 2016; 34:4351–4353 [View Article] [PubMed]
     [Google Scholar]
  5. Kim AH, Hogarty MP, Harris VC, Baldridge MT. The complex interactions between rotavirus and the gut microbiota. Front Cell Infect Microbiol 2020; 10:586751 [View Article] [PubMed]
     [Google Scholar]
  6. Otero CE, Langel SN, Blasi M, Permar SR. Maternal antibody interference contributes to reduced rotavirus vaccine efficacy in developing countries. PLoS Pathog 2020; 16:e1009010 [View Article] [PubMed]
     [Google Scholar]
  7. Church JA, Rukobo S, Govha M, Gough EK, Chasekwa B et al. Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants. EClinicalMedicine 2021; 41:101173 [View Article] [PubMed]
     [Google Scholar]
  8. Bhavnani D, Goldstick JE, Cevallos W, Trueba G, Eisenberg JNS. Synergistic effects between rotavirus and coinfecting pathogens on diarrheal disease: evidence from a community-based study in northwestern Ecuador. Am J Epidemiol 2012; 176:387–395 [View Article] [PubMed]
     [Google Scholar]
  9. Vlasova AN, Amimo JO, Saif LJ. Porcine Rotaviruses: epidemiology, immune responses and control strategies. Viruses 2017; 9:48 [View Article] [PubMed]
     [Google Scholar]
  10. Nemoto M, Hata H, Higuchi T, Imagawa H, Yamanaka T et al. Evaluation of rapid antigen detection kits for diagnosis of equine Rotavirus infection. J Vet Med Sci 2010; 72:1247–1250 [View Article]
     [Google Scholar]
  11. Otto PH, Rosenhain S, Elschner MC, Hotzel H, Machnowska P et al. Detection of rotavirus species A, B and C in domestic mammalian animals with diarrhoea and genotyping of bovine species A Rotavirus strains. Vet Microbiol 2015; 179:168–176 [View Article] [PubMed]
     [Google Scholar]
  12. Bailey KE, Gilkerson JR, Browning GF. Equine rotaviruses--current understanding and continuing challenges. Vet Microbiol 2013; 167:135–144 [View Article] [PubMed]
     [Google Scholar]
  13. Garaicoechea L, Miño S, Ciarlet M, Fernández F, Barrandeguy M et al. Molecular characterization of equine rotaviruses circulating in Argentinean foals during a 17-year surveillance period (1992-2008). Vet Microbiol 2011; 148:150–160 [View Article] [PubMed]
     [Google Scholar]
  14. Dickson J, Smith VW, Coackley W, McKean P, Adams PS. Rotavirus infection of foals. Aust Vet J 1979; 55:207–208 [View Article] [PubMed]
     [Google Scholar]
  15. Imagawa H, Sekiguchi K, Anzai T, Fukunaga Y, Kanemaru T et al. Epidemiology of equine rotavirus infection among foals in the breeding region. J Vet Med Sci 1991; 53:1079–1080 [View Article] [PubMed]
     [Google Scholar]
  16. Slovis NM, Elam J, Estrada M, Leutenegger CM. Infectious agents associated with diarrhoea in neonatal foals in central Kentucky: a comprehensive molecular study. Equine Vet J 2014; 46:311–316 [View Article] [PubMed]
     [Google Scholar]
  17. Carossino M, Barrandeguy ME, Li Y, Parreño V, Janes J et al. Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky. Virus Res 2018; 255:39–54 [View Article] [PubMed]
     [Google Scholar]
  18. Barrandeguy M, Parreño V, Lagos Mármol M, Pont Lezica F, Rivas C et al. Prevention of rotavirus diarrhoea in foals by parenteral vaccination of the mares: field trial. Dev Biol Stand 1998; 92:253–257 [PubMed]
     [Google Scholar]
  19. Saif LJ, Fernandez FM. Group A rotavirus veterinary vaccines. J Infect Dis 1996; 174 Suppl 1:S98–106 [View Article] [PubMed]
     [Google Scholar]
  20. Carossino M, Vissani MA, Barrandeguy ME, Balasuriya UBR, Parreño V. Equine Rotavirus A under the one health lens: potential impacts on public health. Viruses 2024; 16:130 [View Article] [PubMed]
     [Google Scholar]
  21. Hakim MS, Gazali FM, Widyaningsih SA, Parvez MK. Driving forces of continuing evolution of rotaviruses. World J Virol 2024; 13:93774 [View Article] [PubMed]
     [Google Scholar]
  22. Zeller M, Nuyts V, Heylen E, De Coster S, Conceição-Neto N et al. Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era. Sci Rep 2016; 6:36841 [View Article] [PubMed]
     [Google Scholar]
  23. Manjate F, João ED, Mwangi P, Chirinda P, Mogotsi M et al. Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhiça District, Mozambique. Front Microbiol 2023; 14:1193094 [View Article] [PubMed]
     [Google Scholar]
  24. Hoa-Tran TN, Nakagomi T, Vu HM, Nguyen TTT, Dao ATH et al. Evolution of DS-1-like G8P[8] Rotavirus A strains from vietnamese children with acute gastroenteritis (2014-21): Adaptation and loss of animal rotavirus-derived genes during human-to-human spread. Virus Evol 2024; 10:veae045 [View Article] [PubMed]
     [Google Scholar]
  25. Ramig RF. Pathogenesis of intestinal and systemic rotavirus infection. J Virol 2004; 78:10213–10220 [View Article] [PubMed]
     [Google Scholar]
  26. Hyser JM, Estes MK. Rotavirus vaccines and pathogenesis: 2008. Curr Opin Gastroenterol 2009; 25:36–43 [View Article] [PubMed]
     [Google Scholar]
  27. Ruiz MC, Cohen J, Michelangeli F. Role of Ca2+in the replication and pathogenesis of rotavirus and other viral infections. Cell Calcium 2000; 28:137–149 [View Article] [PubMed]
     [Google Scholar]
  28. Gebert JT, Scribano FJ, Engevik KA, Philip AA, Kawagishi T et al. Viroporin activity from rotavirus nonstructural protein 4 induces intercellular calcium waves that contribute to pathogenesis. bioRxiv 20242024.05.07.592929 [View Article] [PubMed]
     [Google Scholar]
  29. Domínguez-Oliva A, Hernández-Ávalos I, Martínez-Burnes J, Olmos-Hernández A, Verduzco-Mendoza A et al. The Importance of animal models in biomedical research: current insights and applications. Animals (Basel) 2023; 13:1223 [View Article] [PubMed]
     [Google Scholar]
  30. Chepngeno J, Takanashi S, Diaz A, Michael H, Paim FC et al. Comparative sequence analysis of historic and current porcine Rotavirus C strains and their pathogenesis in 3-day-old and 3-week-old piglets. Front Microbiol 2020; 11:780 [View Article] [PubMed]
     [Google Scholar]
  31. ADAMS WR, KRAFT LM. Epizootic diarrhea of infant mice: indentification of the etiologic agent. Science 1963; 141:359–360 [View Article] [PubMed]
     [Google Scholar]
  32. Guerrero CA, Santana AY, Acosta O. Mouse intestinal villi as a model system for studies of rotavirus infection. J Virol Methods 2010; 168:22–30 [View Article] [PubMed]
     [Google Scholar]
  33. Ramig RF. The effects of host age, virus dose, and virus strain on heterologous rotavirus infection of suckling mice. Microb Pathog 1988; 4:189–202 [View Article] [PubMed]
     [Google Scholar]
  34. Maffey L, Vega CG, Miño S, Garaicoechea L, Parreño V. Anti-VP6 VHH: an experimental treatment for Rotavirus A-associated disease. PLoS One 2016; 11:e0162351 [View Article] [PubMed]
     [Google Scholar]
  35. Woodyear S, Chandler TL, Kawagishi T, Lonergan TM, Patel VA et al. Chimeric viruses enable study of antibody responses to human Rotaviruses in Mice. Viruses 2024; 16:1145 [View Article] [PubMed]
     [Google Scholar]
  36. Franco MA, Greenberg HB. Immunity to rotavirus infection in mice. J Infect Dis 1999; 179 Suppl 3:S466–9 [View Article] [PubMed]
     [Google Scholar]
  37. Carossino M, Balasuriya UBR, Thieulent CJ, Barrandeguy ME, Vissani MA et al. Quadruplex real-time TaqMan® RT-qPCR assay for differentiation of equine group A and B Rotaviruses and identification of group A G3 and G14 genotypes. Viruses 2023; 15:1626 [View Article] [PubMed]
     [Google Scholar]
  38. Ramakrishnan MA. Determination of 50% endpoint titer using a simple formula. World J Virol 2016; 5:85–86 [View Article] [PubMed]
     [Google Scholar]
  39. Carossino M, Barrandeguy ME, Erol E, Li Y, Balasuriya UBR. Development and evaluation of a one-step multiplex real-time TaqMan® RT-qPCR assay for the detection and genotyping of equine G3 and G14 rotaviruses in fecal samples. Virol J 2019; 16:49 [View Article] [PubMed]
     [Google Scholar]
  40. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69:238–249 [PubMed]
     [Google Scholar]
  41. Kwon T, Trujillo JD, Carossino M, Lyoo EL, McDowell CD et al. Pigs are highly susceptible to but do not transmit mink-derived highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b. Emerg Microbes Infect 2024; 13:2353292 [View Article] [PubMed]
     [Google Scholar]
  42. Coelho KI, Bryden AS, Hall C, Flewett TH. Pathology of rotavirus infection in suckling mice: a study by conventional histology, immunofluorescence, ultrathin sections, and scanning electron microscopy. Ultrastruct Pathol 1981; 2:59–80 [View Article] [PubMed]
     [Google Scholar]
  43. Offor E, Riepenhoff-Talty M, Ogra PL. Effect of malnutrition on rotavirus infection in suckling mice: kinetics of early infection. Proc Soc Exp Biol Med 1985; 178:85–90 [View Article] [PubMed]
     [Google Scholar]
  44. Hao P, Pang Z, Qu Q, Cui C, Jiang Y et al. A G3P[3] bat rotavirus can infect cultured human cholangiocytes and cause biliary atresia symptom in suckling mice. Virol Sin 2024; 39:974–976 [View Article] [PubMed]
     [Google Scholar]
  45. Nemoto M, Inagaki M, Tamura N, Bannai H, Tsujimura K et al. Evaluation of inactivated vaccines against equine group A rotaviruses by use of a suckling mouse model. Vaccine 2018; 36:5551–5555 [View Article] [PubMed]
     [Google Scholar]
  46. Offit PA, Clark HF. Maternal antibody-mediated protection against gastroenteritis due to rotavirus in newborn mice is dependent on both serotype and titer of antibody. J Infect Dis 1985; 152:1152–1158 [View Article] [PubMed]
     [Google Scholar]
  47. Coste A, Sirard JC, Johansen K, Cohen J, Kraehenbuhl JP. Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea. J Virol 2000; 74:8966–8971 [View Article] [PubMed]
     [Google Scholar]
  48. Meier AF, Suter M, Schraner EM, Humbel BM, Tobler K et al. Transfer of anti-rotavirus antibodies during pregnancy and in Milk following maternal vaccination with a herpes simplex virus type-1 amplicon vector. Int J Mol Sci 2017; 18:431 [View Article] [PubMed]
     [Google Scholar]
  49. Xue M, Yu L, Jia L, Li Y, Zeng Y et al. Immunogenicity and protective efficacy of rotavirus VP8* fused to cholera toxin B subunit in a mouse model. Hum Vaccin Immunother 2016; 12:2959–2968 [View Article] [PubMed]
     [Google Scholar]
  50. Franco MA, Tin C, Greenberg HB. CD8+ T cells can mediate almost complete short-term and partial long-term immunity to rotavirus in mice. J Virol 1997; 71:4165–4170 [View Article] [PubMed]
     [Google Scholar]
  51. Malamba-Banda C, Mhango C, Benedicto-Matambo P, Mandolo JJ, Chinyama E et al. Acute rotavirus infection is associated with the induction of circulating memory CD4+ T cell subsets. Sci Rep 2023; 13:9001 [View Article] [PubMed]
     [Google Scholar]
  52. Knipping K, McNeal MM, Crienen A, van Amerongen G, Garssen J et al. A gastrointestinal rotavirus infection mouse model for immune modulation studies. Virol J 2011; 8:109 [View Article] [PubMed]
     [Google Scholar]
  53. Angel J, Franco MA, Greenberg HB. Rotavirus immune responses and correlates of protection. Curr Opin Virol 2012; 2:419–425 [View Article] [PubMed]
     [Google Scholar]
  54. Sánchez-Tacuba L, Kawagishi T, Feng N, Jiang B, Ding S et al. The role of the VP4 attachment protein in rotavirus host range restriction in an In Vivo suckling mouse model. J Virol 2022; 96:e0055022 [View Article] [PubMed]
     [Google Scholar]
  55. Feng N, Lawton JA, Gilbert J, Kuklin N, Vo P et al. Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific IgA mAb. J Clin Invest 2002; 109:1203–1213 [View Article] [PubMed]
     [Google Scholar]
  56. VanCott JL, Prada AE, McNeal MM, Stone SC, Basu M et al. Mice develop effective but delayed protective immune responses when immunized as neonates either intranasally with nonliving VP6/LT(R192G) or orally with live rhesus rotavirus vaccine candidates. J Virol 2006; 80:4949–4961 [View Article] [PubMed]
     [Google Scholar]
  57. Du J, Lan Z, Liu Y, Liu Y, Li Y et al. Detailed analysis of BALB/c mice challenged with wild type rotavirus EDIM provide an alternative for infection model of rotavirus. Virus Res 2017; 228:134–140 [View Article] [PubMed]
     [Google Scholar]
  58. McNeal MM, Rae MN, Ward RL. Evidence that resolution of rotavirus infection in mice is due to both CD4 and CD8 cell-dependent activities. J Virol 1997; 71:8735–8742 [View Article] [PubMed]
     [Google Scholar]
  59. Ciarlet M, Estes MK, Barone C, Ramig RF, Conner ME. Analysis of host range restriction determinants in the rabbit model: comparison of homologous and heterologous rotavirus infections. J Virol 1998; 72:2341–2351 [View Article] [PubMed]
     [Google Scholar]
  60. Boshuizen JA, Reimerink JHJ, Korteland-van Male AM, van Ham VJJ, Koopmans MPG et al. Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice. J Virol 2003; 77:13005–13016 [View Article] [PubMed]
     [Google Scholar]
  61. Rollo EE, Kumar KP, Reich NC, Cohen J, Angel J et al. The epithelial cell response to rotavirus infection. J Immunol 1999; 163:4442–4452 [PubMed]
     [Google Scholar]
  62. Yan M, Su A, Pavasutthipaisit S, Spriewald R, Graßl GA et al. Infection of porcine enteroids and 2D differentiated intestinal epithelial cells with Rotavirus A to study cell tropism and polarized immune response. Emerg Microbes Infect 2023; 12:2239937 [View Article] [PubMed]
     [Google Scholar]
  63. Li Y, Liu D, Wang Y, Su W, Liu G et al. The importance of glycans of viral and host proteins in enveloped virus infection. Front Immunol 2021; 12:638573 [View Article]
     [Google Scholar]
  64. Semmes EC, Chen J-L, Goswami R, Burt TD, Permar SR et al. Understanding early-life adaptive immunity to guide interventions for pediatric health. Front Immunol 2020; 11:595297 [View Article] [PubMed]
     [Google Scholar]
  65. Perkins GA, Wagner B. The development of equine immunity: current knowledge on immunology in the young horse. Equine Vet J 2015; 47:267–274 [View Article] [PubMed]
     [Google Scholar]
/content/journal/jgv/10.1099/jgv.0.002110
Loading
Comparative clinical, virological and pathological characterization of equine rotavirus A G3P[12] and G14P[12] infection in neonatal mice
J. Gen. Virol. 106, 002110 (2025); https://doi.org/10.1099/jgv.0.002110
/content/journal/jgv/10.1099/jgv.0.002110
/content/journal/jgv/10.1099/jgv.0.002110
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An error occurred
Approval was partially successful, following selected items could not be processed due to error