Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro

Erika Faber; Selaelo Ivy Tshilwane; Mirinda Van Kleef; Alri Pretorius

doi:10.1016/j.meegid.2021.104836

Virulent African horse sickness virus serotype 4 interferes with the innate immune response in horse peripheral blood mononuclear cells in vitro

Infect Genet Evol. 2021 Jul:91:104836. doi: 10.1016/j.meegid.2021.104836. Epub 2021 Mar 31.

Authors

Erika Faber¹, Selaelo Ivy Tshilwane², Mirinda Van Kleef³, Alri Pretorius³

Affiliations

¹ 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.
² School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
³ 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.

PMID: 33798756
DOI: 10.1016/j.meegid.2021.104836

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.

Keywords: AHSV; Antiviral treatment; Immune evasion; Immunopathology; Innate immune response; Transcriptome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

African Horse Sickness / immunology*
African Horse Sickness / virology
African Horse Sickness Virus / physiology*
Animals
Horses
Immunity, Innate*
Leukocytes, Mononuclear / virology*
Serogroup