Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China.
CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, China.
Viruses. 2024 Sep 16;16(9):1472. doi: 10.3390/v16091472.
Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.
马疱疹病毒 1 型（EHV-1）已被证实与神经紊乱的出现有关，赛马行业因马疱疹病毒脑脊髓炎（EHM）的爆发而受到重大影响。在病原体暴露前建立强大的免疫记忆可以实现快速识别和消除，从而预防感染。这对于有效管理 EHV-1 至关重要。去除神经致病性因子和免疫逃逸基因以开发活减毒疫苗似乎是 EHV-1 疫苗的成功策略。我们构建了缺失 ORF38 和 ORF37/38 的突变病毒，并在仓鼠中验证了它们的神经致病性和免疫原性。高剂量下，∆ORF38 株会引起脑组织损伤，而 ∆ORF37/38 株则不会。地塞米松用于确认潜伏性疱疹病毒感染和再激活。地塞米松注射会增加感染亲本株和 ∆ORF38 株的仓鼠脑中的病毒 DNA 载量，但不会增加感染 ∆ORF37/38 株的仓鼠脑中的病毒 DNA 载量。用 ∆ORF37/38 株作为活疫苗经鼻腔免疫仓鼠会产生比 ∆ORF38 株更强的免疫反应，尽管剂量相同。仓鼠对亲本株的致死性攻击表现出有效保护。这表明 ORF37/38 的缺失可能有效抑制潜伏性病毒感染，降低 EHV-1 的神经致病性，并诱导保护性免疫反应。
