Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro.
Abstract: African horse sickness (AHS) is caused by African horse sickness virus (AHSV), a double stranded RNA (dsRNA) virus of the genus Orbivirus, family Reoviridae. For the development of new generation AHS vaccines or antiviral treatments, it is crucial to understand the host immune response against the virus and the immune evasion strategies the virus employs. To achieve this, the current study used transcriptome analysis of RNA sequences to characterize and compare the innate immune responses activated during the attenuated AHSV serotype 4 (attAHSV4) (in vivo) and the virulent AHSV4 (virAHSV4) (in vitro) primary and secondary immune responses in horse peripheral blood mononuclear cells (PBMC) after 24 h. The pro-inflammatory cytokine and chemokine responses were negatively regulated by anti-inflammatory cytokines, whereas the parallel type I and type III IFN responses were maintained downstream of nucleic acid sensing pattern recognition receptor (PRR) signalling pathways during the attAHSV4 primary and secondary immune responses. It appeared that after translation, virAHSV4 proteins were able to interfere with the C-terminal IRF association domain (IAD)-type 1 (IAD1) containing IRFs, which inhibited the expression of type I and type III IFNs downstream of PRR signalling during the virAHSV4 primary and secondary immune responses. Viral interference resulted in an impaired innate immune response that was not able to eliminate virAHSV4-infected PBMC and gave rise to prolonged expression of pro-inflammatory cytokines and chemokines during the virAHSV4 induced primary immune response. Indicating that virAHSV4 interference with the innate immune response may give rise to an excessive inflammatory response that causes immunopathology, which could be a major contributing factor to the pathogenesis of AHS in a naïve horse. Viral interference was overcome by the fast kinetics and increased effector responses of innate immune cells due to trained innate immunity and memory T cells and B cells during the virAHSV4 secondary immune response.
Copyright © 2021 Elsevier B.V. All rights reserved.
Publication Date: 2021-03-31 PubMed ID: 33798756DOI: 10.1016/j.meegid.2021.104836Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article presents a study on how the virulent African horse sickness virus (AHSV) interferes with the innate immune response in horses. The study reveals that the virus can hinder the immune response, which can lead to an excessive inflammatory reaction that may be majorly responsible for the sickness in naïve horses.
Understanding the Study
- The study was conducted to understand the host immune response against African horse sickness virus (AHSV). This knowledge will help in designing new generation vaccines or antiviral treatments for the disease.
- AHSV is a double-stranded RNA virus of the Reoviridae family and Orbivirus genus, and is the cause of African horse sickness (AHS).
- The researchers used transcriptome analysis of RNA sequences to explore and compare the immune responses activated by an attenuated AHSV serotype 4 in vivo, and a virulent AHSV4 in vitro.
Cytokine Responses
- The analysis revealed that the pro-inflammatory cytokine and chemokine responses were negatively regulated by anti-inflammatory cytokines in case of attAHSV4 induced immune responses. Both type I and type III IFN responses were observed downstream of PRR (Pattern Recognition Receptor) signalling pathways, which senses nucleic acids.
- However, in the case of virulent AHSV4 induced primary and secondary immune responses, it was observed that the post translation virAHSV4 proteins interfered with the C-terminal IRF association domain (IAD)-type 1 containing IRFs, leading to inhibition of type I and III IFN responses downstream of PRR signalling.
Viral Interference and Immune Response
- The viral interference resulted in an impaired immune response, which was not effective in eliminating AHSV-infection in the peripheral blood mononuclear cells (PBMC). This led to prolonged expression of pro-inflammatory cytokines and chemokines.
- It was suggested that this viral interference could give rise to an excessive inflammatory response which may contribute to the pathogenesis of AHS in naïve horses.
Overcoming Viral Interference
- The article further suggests that the viral interference was overcome by the faster pace and increased effector responses of the innate immune cells, memory T cells, and B cells, during the secondary immune response induced by virulent AHSV4.
- This indicates that trained innate immunity and memory cells have the potential to counter the effects of viral interference in the immune response.
Cite This Article
APA
Faber E, Tshilwane SI, Kleef MV, Pretorius A.
(2021).
Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro.
Infect Genet Evol, 91, 104836.
https://doi.org/10.1016/j.meegid.2021.104836 Publication
Researcher Affiliations
- Agricultural Research Council - Onderstepoort Veterinary Research, Private Bag X5, Onderstepoort 0110, South Africa; Department of Veterinary Tropical Disease, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa. Electronic address: FaberE@arc.agric.za.
- School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
- Agricultural Research Council - Onderstepoort Veterinary Research, Private Bag X5, Onderstepoort 0110, South Africa; Department of Veterinary Tropical Disease, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
- Agricultural Research Council - Onderstepoort Veterinary Research, Private Bag X5, Onderstepoort 0110, South Africa; Department of Veterinary Tropical Disease, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
MeSH Terms
- African Horse Sickness / immunology
- African Horse Sickness / virology
- African Horse Sickness Virus / physiology
- Animals
- Horses
- Immunity, Innate
- Leukocytes, Mononuclear / virology
- Serogroup
Citations
This article has been cited 3 times.- 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).
- Jones LM, Hawes PC, Salguero FJ, Castillo-Olivares J. Pathological features of African horse sickness virus infection in IFNAR(-/-) mice. Front Vet Sci 2023;10:1114240.
- Clemmons EA, Alfson KJ, Dutton JW 3rd. Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences. Animals (Basel) 2021 Jul 8;11(7).
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