Intranasal treatment with CpG-B oligodeoxynucleotides protects CBA mice from lethal equine herpesvirus 1 challenge by an innate immune response

• Published in: Antiviral research 2019-09, Vol.169, p.104546-104546, Article 104546
• Main Authors: Kim, Seong K., Shakya, Akhalesh K., O'Callaghan, Dennis J.
• Format: Article
• Language: English
• Subjects: CBA mice; CpG-B ODN 1826; Equine herpesvirus 1; IFN-γ; Innate immune response; Interferon-stimulated genes; Oligodeoxynucleotides
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2019.104546

Equine herpesvirus 1 (EHV-1) is the causative agent of a number of equine disease manifestations, including severe disease of the central nervous system, respiratory infections, and abortion storms. Our results showed that intranasal treatment with CpG-B oligodeoxynucleotides (ODN 1826) protected CBA mice from pathogenic EHV-1 RacL11 challenge. The IFN-γ gene and seven interferon-stimulated genes (ISGs) were upregulated 39.4- to 260.3-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been treated with CpG-B ODN. Interestingly, IFN-γ gene expression was upregulated by 26-fold upon RacL11 challenge in CpG-B ODN-treated mice lungs as compared to that of CpG-A ODN (ODN 1585)-treated mice lungs; however, the seven ISGs were upregulated by 2.4–5.0-fold, suggesting that IFN-γ is a major factor in the protection of CBA mice from the lethal challenge. Pre-treatment with IFN-γ significantly reduced EHV-1 yield in murine alveolar macrophage MH-S cells, but not in mouse lung epithelial MLE12 cells. These results suggest that CpG-B ODN may be used as a prophylactic agent in horses and provide a basis for more effective treatment of EHV-1 infection. •Treatment with CpG-B ODN significantly upregulated IFN-γ and seven antiviral ISGs upon lethal EHV-1 challenge.•CpG-B treatment protected CBA mice from lethal EHV-1 challenge.•Pre-treatment with IFN-γ reduced EHV-1 yield by ∼1200-fold in MH-S cells, but by 4-fold in MLE12 cells.•These results demonstrated that CpG-B ODN may serve as a novel prophylactic agent.