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Home / Equine Research Bank / Front Vet Sci / Pathological features of African horse sickness virus infect...
Frontiers in veterinary science2023; 10; 1114240; doi: 10.3389/fvets.2023.1114240

Pathological features of African horse sickness virus infection in IFNAR-/- mice.

Abstract: African Horse Sickness (AHS) is a vector-borne viral disease of equids. The disease can be highly lethal with mortality rates of up to 90% in non-immune equine populations. The clinical presentation in the equine host varies, but the pathogenesis underlying this variation remains incompletely understood. Various small animal models of AHS have been developed over the years to overcome the financial, bio-safety and logistical constraints of studying the pathology of this disease in the target species. One of the most successful small animal models is based on the use of interferon-alpha gene knock-out (IFNAR-/-) mice. In order to increase our understanding of African Horse Sickness virus (AHSV) pathogenesis, we characterised the pathology lesions of AHSV infection in IFNAR-/- mice using a strain of AHSV serotype 4 (AHSV-4). We found AHSV-4 infection was correlated with lesions in various organs; necrosis in the spleen and lymphoid tissues, inflammatory infiltration in the liver and brain, and pneumonia. Significant viral antigen staining was only detected in the spleen and brain, however. Together these results confirm the value of the IFNAR-/- mouse model for the study of the immuno-biology of AHSV infections in this particular in vivo system, and its usefulness for evaluating protective efficacy of candidate vaccines in preclinical studies.
Copyright © 2023 Jones, Hawes, Salguero and Castillo-Olivares.
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Publication Date: 2023-03-30 PubMed ID: 37065248PubMed Central: PMC10098166DOI: 10.3389/fvets.2023.1114240Google Scholar: Lookup
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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.

The research conducted a detailed examination of the pathological effects of African Horse Sickness virus (AHSV) in IFNAR mice, which underscored the value of this mouse model for studying the disease and evaluating potential vaccines.

Background:

  • African Horse Sickness (AHS) is a viral disease of equids (horses, donkeys and the like) which is transmitted by vectors, in this case, insects.
  • It is a highly fatal disease without adequate immunity, with mortality rates shooting up to approximately 90% in non-immune equine populations.
  • There is significant variation in the clinical presentation of AHS in equine hosts, but the pathogenesis – or the biological mechanism that leads to the disease – remains incompletely understood.
  • Small animal models have been developed over the years to effectively study the pathology of AHS because carrying out similar studies in target species has been challenging due to financial, bio-safety and logistical constraints.
  • One such effective model is based on the use of interferon-alpha gene knock-out, commonly referred to as IFNAR mice.

Research Methods and Findings:

  • The researchers used a specific strain of AHSV, serotype 4 (AHSV-4), to infect IFNAR mice, aiming to increase the understanding of AHSV’s pathogenetic mechanisms.
  • Post-infection, they performed detailed characterization of the pathology lesions in these mice.
  • They discovered that AHSV-4 infection in IFNAR mice was associated with lesions in various organs: it caused necrosis in the spleen and lymphoid tissues, prompted inflammatory infiltration in the liver and brain, and also induced pneumonia.
  • Worthy of note is the fact that significant viral antigen staining was only detected in the spleen and brain, indicating these locations as key sites of viral activity.

Conclusion:

  • The study reaffirms the value and viability of the IFNAR mouse model for studying AHSV infections, specifically, understanding immune responses to the virus.
  • This model also proves useful for assessing the protective efficacy of potential vaccines in preclinical studies, serving as an accessible and efficient platform for preliminary testing and advancement of AHS management strategies.

Cite This Article

APA
Jones LM, Hawes PC, Salguero FJ, Castillo-Olivares J. (2023). Pathological features of African horse sickness virus infection in IFNAR-/- mice. Front Vet Sci, 10, 1114240. https://doi.org/10.3389/fvets.2023.1114240

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 10
Pages: 1114240

Researcher Affiliations

Jones, Luke M
  • The Pirbright Institute, Woking, United Kingdom.
Hawes, Phillippa C
  • The Pirbright Institute, Woking, United Kingdom.
Salguero, Francisco J
  • United Kingdom Health Security Agency, UKHSA-Porton Down, Salisbury, United Kingdom.
  • School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom.
Castillo-Olivares, Javier
  • The Pirbright Institute, Woking, United Kingdom.
  • Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.

Grant Funding

  • BBS/E/I/00007037 / Biotechnology and Biological Sciences Research Council

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 43 references
  1. Baylis M, Hasnaoui HE, Bouayoune H, Touti J, Mellor P. the spatial and seasonal distribution of african horse sickness and its potential culicoides vectors in Morocco. Med Vet Entomol (1997) 11:203–12.
    doi: 10.1111/j.1365-2915.1997.tb00397.xpubmed: 9330250google scholar: lookup
  2. Rodriguez M, Hooghuis H, Castaño M. African horse sickness in Spain. Vet Microbiol (1992) 33:129–42.
    doi: 10.1016/0378-1135(92)90041-Qpubmed: 1481352google scholar: lookup
  3. Portas M, Boinas F, Sousa JOE, Rawlings P. African horse sickness in portugal: a successful eradication programme. Epidemiol Inf (1999) 123:337–46.
    doi: 10.1017/S0950268899002897pmc: PMC2810767pubmed: 10579455google scholar: lookup
  4. Cêtre-Sossah C, Baldet T, Delécolle J-C, Mathieu B, Perrin A, Grillet C. Molecular Detection of Culicoides Spp. and culicoides imicola, the principal vector of bluetongue (Bt) and African horse sickness (Ahs) in Africa and Europe. Vet Res (2004) 35:325–37.
    doi: 10.1051/vetres:2004015pubmed: 15210081google scholar: lookup
  5. Mellor P, Boorman J. The Transmission and geographical spread of african horse sickness and bluetongue viruses. Annal Trop Med Parasitol (1995) 89:1–15.
    doi: 10.1080/00034983.1995.11812923pubmed: 7741589google scholar: lookup
  6. Mellor PS, Hamblin C. African horse sickness. Vet Res (2004) 35:445–66.
    doi: 10.1051/vetres:2004021pubmed: 15236676google scholar: lookup
  7. O'Hara R, Meyer A, Burroughs J, Pullen L, Martin L-A, Mertens P. Development of a Mouse Model System, Coding Assignments and Identification of the Genome Segments Controlling Virulence of African Horse Sickness Virus Serotypes 3 and 8. Veinna: Springer; (1998). p. 259–79.
    pubmed: 9785512
  8. Burrage T, Laegreid W. African horsesickness: pathogenesis and immunity. Comp Immunol Microbiol Infect Dis (1994) 17:275–85.
    doi: 10.1016/0147-9571(94)90047-7pubmed: 8001349google scholar: lookup
  9. Bremer C. A. Gel electrophoretic study of the protein and nucleic acid components of african horsesickness virus. Onderstepoort J Vet Res (1976) 43:193–9.
    pubmed: 1023091
  10. Bremer CW, Huismans H, Van Dijk AA. Characterization and cloning of the african horsesickness virus genome. J Gen Virol (1990) 71:793–9.
    doi: 10.1099/0022-1317-71-4-793pubmed: 2324709google scholar: lookup
  11. Manole V, Laurinmäki P, Van Wyngaardt W, Potgieter CA, Wright IM, Venter GJ. Structural insight into african horsesickness virus infection. J Virol (2012) 86:7858–66.
    doi: 10.1128/JVI.00517-12pmc: PMC3421665pubmed: 22593166google scholar: lookup
  12. Sailleau C, Hamblin C, Paweska J, Zientara S. Identification and differentiation of the nine african horse sickness virus serotypes by Rt–Pcr amplification of the serotype-specific genome segment 2. J Gen Virol (2000) 81:831–7.
    doi: 10.1099/0022-1317-81-3-831pubmed: 10675421google scholar: lookup
  13. Clift S, Penrith M-L. Tissue and cell tropism of african horse sickness virus demonstrated by immunoperoxidase labeling in natural and experimental infection in horses in south Africa. Veterinary Pathol (2010) 47:690–7.
    doi: 10.1177/0300985810370010pubmed: 20484177google scholar: lookup
  14. Gomez-Villamandos J, Sanchez C, Carrasco L, Laviada M, Bautista M, Martinez-Torrecuadrada J. Pathogenesis of african horse sickness: ultrastructural study of the capillaries in experimental infection. J Comp Pathol (1999) 121:101–16.
    doi: 10.1053/jcpa.1999.0305pubmed: 10405303google scholar: lookup
  15. Carrasco L, Sanchez C, Gomez-Villamandos J, Laviada M, Bautista M, Martinez-Torrecuadrada J. The role of pulmonary intravascular macrophages in the pathogenesis of african horse sickness. J Comp Pathol (1999) 121:25–38.
    doi: 10.1053/jcpa.1998.0293pubmed: 10373291google scholar: lookup
  16. Wohlsein P, Pohlenz J, Salt J, Hamblin C. Immunohistochemical Demonstration of African Horse Sickness Viral Antigen in Tissues of Experimentally Infected Equines. African Horse Sickness. Veinna: Springer; (1998). p. 57–65.
    pubmed: 9785496
  17. Brown C, Meyer R, Grubman M. Presence of african horse sickness virus in equine tissues, as determined by in situ hybridization. Vet Pathol (1994) 31:689–94.
    doi: 10.1177/030098589403100609pubmed: 7863585google scholar: lookup
  18. Erasmus B. The Pathogenesis of African Horsesickness. Equine Infectious Diseases. Basel: Karger Publishers; (1974). p. 1–11.
  19. Faber E, Tshilwane SI, Van Kleef M, Pretorius A. Apoptosis versus survival of african horse sickness virus serotype 4-infected horse peripheral blood mononuclear cells. Virus Res (2022) 307:198609.
    doi: 10.1016/j.virusres.2021.198609pubmed: 34688785google scholar: lookup
  20. Castillo-Olivares J, Calvo-Pinilla E, Casanova I, Bachanek-Bankowska K, Chiam R, Maan S. A modified vaccinia ankara virus (Mva) vaccine expressing african horse sickness virus (Ahsv) Vp2 protects against AHSV challenge in an Ifnar–/– mouse model. PLoS ONE (2011) 6:e16503.
    doi: 10.1371/journal.pone.0016503pmc: PMC3027694pubmed: 21298069google scholar: lookup
  21. Muller U, Steinhoff U, Reis L, Hemmi S, Pavlovic J, Zinkernagel RM. Functional role of type i and type ii interferons in antiviral defense. Science (1994) 264:1918–21.
    doi: 10.1126/science.8009221pubmed: 8009221google scholar: lookup
  22. Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S. The ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo. PLoS Pathog (2012) 8:e1002847.
    doi: 10.1371/journal.ppat.1002847pmc: PMC3410889pubmed: 22876185google scholar: lookup
  23. Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ. A mouse model of zika virus pathogenesis. Cell Host Microbe (2016) 19:720–30.
    doi: 10.1016/j.chom.2016.03.010pmc: PMC4866885pubmed: 27066744google scholar: lookup
  24. Calvo-Pinilla E, Rodríguez-Calvo T, Anguita J, Sevilla N, Ortego J. Establishment of a bluetongue virus infection model in mice that are deficient in the alpha/beta interferon receptor. PLoS ONE (2009) 4:e5171.
    doi: 10.1371/journal.pone.0005171pmc: PMC2663843pubmed: 19357779google scholar: lookup
  25. Jabbar TK, Calvo-Pinilla E, Mateos F, Gubbins S, Bin-Tarif A, Bachanek-Bankowska K. Protection of Ifnar (–/–) mice against bluetongue virus serotype 8, by heterologous (DNA/Rmva) and homologous (Rmva/Rmva) vaccination, expressing outer-capsid protein Vp2. PLoS ONE (2013) 8:e60574.
    doi: 10.1371/journal.pone.0060574pmc: PMC3625202pubmed: 23593251google scholar: lookup
  26. Aksular M, Calvo-Pinilla E, Marín-López A, Ortego J, Chambers AC, King LA. A single dose of african horse sickness virus (Ahsv) Vp2 based vaccines provides complete clinical protection in a mouse model. Vaccine (2018) 36:7003–10.
    doi: 10.1016/j.vaccine.2018.09.065pmc: PMC6219453pubmed: 30309744google scholar: lookup
  27. Calvo-Pinilla E, de la Poza F, Gubbins S, Mertens PPC, Ortego J, Castillo-Olivares J. Vaccination of mice with a modified vaccinia ankara (Mva) virus expressing the african horse sickness virus (Ahsv) capsid protein vp2 induces virus neutralising antibodies that confer protection against ahsv upon passive immunisation virus research. J Virus (2014) 180:23–30.
    doi: 10.1016/j.virusres.2013.12.002pubmed: 24333835google scholar: lookup
  28. Calvo-Pinilla E, de la Poza F, Gubbins S, Mertens PPC, Ortego J, Castillo-Olivares J. Antiserum from mice vaccinated with modified vaccinia ankara virus expressing african horse sickness virus (Ahsv) Vp2 provides protection when it is administered 48 H before, or 48 H after challenge. Antiviral Res (2015) 116:27–33.
    doi: 10.1016/j.antiviral.2015.01.009pmc: PMC7125940pubmed: 25643968google scholar: lookup
  29. Calvo-Pinilla E, Gubbins S, Mertens P, Ortego J, Castillo-Olivares J. The immunogenicity of recombinant vaccines based on modified vaccinia ankara (Mva) viruses expressing african horse sickness virus vp2 antigens depends on the levels of expressed vp2 protein delivered to the host. Antiviral Res (2018) 154:132–9.
    doi: 10.1016/j.antiviral.2018.04.015pmc: PMC5966619pubmed: 29678552google scholar: lookup
  30. Bekker S, Huismans H, van Staden V. Factors that affect the intracellular localization and trafficking of african horse sickness virus core protein, Vp7. Virology (2014) 456:279–91.
    doi: 10.1016/j.virol.2014.03.030pubmed: 24889247google scholar: lookup
  31. de la Poza F, Calvo-Pinilla E, López-Gil E, Marín-López A, Mateos F, Castillo-Olivares J. Ns1 is a key protein in the vaccine composition to protect Ifnar (–/–) mice against infection with multiple serotypes of african horse sickness virus. PloS ONE (2013) 8:e70197.
    doi: 10.1371/journal.pone.0070197pmc: PMC3720900pubmed: 23894615google scholar: lookup
  32. Alberca B, Bachanek-Bankowska K, Cabana M, Calvo-Pinilla E, Viaplana E, Frost L. Vaccination of horses with a recombinant modified vaccinia ankara virus (Mva) expressing african horse sickness (Ahs) virus major capsid protein vp2 provides complete clinical protection against challenge. Vaccine (2014) 32:3670–4.
    doi: 10.1016/j.vaccine.2014.04.036pmc: PMC4061461pubmed: 24837765google scholar: lookup
  33. Newsholme SJ. A morphological study of the lesions of african horsesickness. J Vet Res (1983) 50:48.
    pubmed: 6877796
  34. Faber E, Tshilwane SI, Van Kleef M, Pretorius A. Virulent african horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro. Inf Gen Evol (2021) 91:104836.
    doi: 10.1016/j.meegid.2021.104836pubmed: 33798756google scholar: lookup
  35. Mirchamsy H, Hazrati A. A review on aetiology and pathogeny of african horse sickness. Arch Razi Inst (1973) 25:23–46.
  36. Greenhalgh AD, Zarruk JG, Healy LM, Jesudasan SJB, Jhelum P, Salmon CK. Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury. PLoS Biol (2018) 16:e2005264.
    doi: 10.1371/journal.pbio.2005264pmc: PMC6205650pubmed: 30332405google scholar: lookup
  37. Lahrtz F, Piali L, Spanaus K-S, Seebach J, Fontana A. Chemokines and chemotaxis of leukocytes in infectious meningitis. J Neuroimmunol (1998) 85:33–43.
    doi: 10.1016/S0165-5728(97)00267-1pubmed: 9626995google scholar: lookup
  38. Laegreid W, Burrage T, Stone-Marschat M, Skowronek A. Electron microscopic evidence for endothelial infection by african horsesickness virus. Vet Pathol (1992) 29:554–6.
    doi: 10.1177/030098589202900615pubmed: 1448905google scholar: lookup
  39. Maclachlan NJ, Henderson C, Schwartz-Cornil I, Zientara S. The immune response of ruminant livestock to bluetongue virus: from type i interferon to antibody. Virus Res (2014) 182:71–7.
    doi: 10.1016/j.virusres.2013.09.040pubmed: 24120757google scholar: lookup
  40. Howerth EW. Cytokine release and endothelial dysfunction: a perfect storm in orbivirus pathogenesis. Vet Ital (2015) 51:275–81.
    doi: 10.12834/VetIt.593.2854.1pubmed: 26741244google scholar: lookup
  41. Schwartz-Cornil I, Mertens PP, Contreras V, Hemati B, Pascale F, Bréard E. Bluetongue virus: virology, pathogenesis and immunity. Vet Res (2008) 39:1.
    doi: 10.1051/vetres:2008023pubmed: 18495078google scholar: lookup
  42. Carrasco L, Ruiz-Villamor E, Gomez-Villamandos J, Salguero F, Bautista M, Macia M. Classical swine fever: morphological and morphometrical study of pulmonary intravascular macrophages. J Comp Pathol (2001) 125:1–7.
    doi: 10.1053/jcpa.2001.0470pubmed: 11437510google scholar: lookup
  43. Jones LM. Understanding the Basis for African Horse Sickness Virus Pathogenicity Using a Murine Infection Model. Surrey: University of Surrey; (2021).

Citations

This article has been cited 2 times.
  1. Jiménez-Cabello L, Utrilla-Trigo S, Benavides-Silván J, Anguita J, Calvo-Pinilla E, Ortego J. IFNAR(-/-) Mice Constitute a Suitable Animal Model for Epizootic Hemorrhagic Disease Virus Study and Vaccine Evaluation. Int J Biol Sci 2024;20(8):3076-3093.
    doi: 10.7150/ijbs.95275pubmed: 38904031google scholar: lookup
  2. Calvo-Pinilla E, Jiménez-Cabello L, Utrilla-Trigo S, Illescas-Amo M, Ortego J. Cytokine mRNA Expression Profile in Target Organs of IFNAR (-/-) Mice Infected with African Horse Sickness Virus. Int J Mol Sci 2024 Feb 8;25(4).
    doi: 10.3390/ijms25042065pubmed: 38396742google scholar: lookup
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