Xu Lei, Wei Jian-Feng, Zhao Jun, Xu Si-Yao, Lee Feng-Qin, Nie Min-Cai, Xu Zhi-Wen, Zhou Yuan-Cheng, Zhu Ling
Key Laboratory of Animal Diseases and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China.
Front Microbiol. 2022 Mar 25;13:862907. doi: 10.3389/fmicb.2022.862907. eCollection 2022.
Based on a variant strain, we constructed a gE/gI/TK-deleted pseudorabies virus (PRV). A total of 18 female mice were randomized to a vaccination group to receive PRV XJ delgE/gI/TK, a vehicle group to receive Dulbecco's modified Eagle's medium, and a mock group to confirm the protection of PRV delgE/gI/TK on the central nervous system in mice. Subsequently, the vaccination and vehicle groups were infected with PRV XJ. The mice in the vehicle group showed more severe neurological symptoms and higher viral loads than those in the vaccination group. The exudation of Evans blue and the expression of tight junction protein showed no difference in all groups. HE staining showed vacuolar neuronal degeneration in the vehicle group brain, but no tissue lesions were observed in the vaccination group. TNF-α, IL-6, and synuclein were upregulated in the brain of mice in the vehicle group, while those were inhibited among mice in the vaccination group. IFN-β, IFN-γ, ISG15, Mx1, and OAS1 showed no difference in the brain between the vaccination and vehicle groups. In addition, TNF-α and IL-6 were inhibited, and antiviral factors were increased in the intestine of the mice in the vaccination group compared to those in the vehicle group. Our study showed that PRV XJ delgE/gI/TK inhibited neurological damage and the inflammation of the intestine and brain induced by PRV and activated the innate immunity of the intestine.
基于一株变异毒株,我们构建了一种缺失gE/gI/TK的伪狂犬病病毒(PRV)。总共18只雌性小鼠被随机分为疫苗接种组,接受PRV XJ delgE/gI/TK;载体组,接受杜氏改良 Eagle培养基;以及模拟组,以确认PRV delgE/gI/TK对小鼠中枢神经系统的保护作用。随后,疫苗接种组和载体组感染PRV XJ。载体组小鼠比疫苗接种组小鼠表现出更严重的神经症状和更高的病毒载量。伊文思蓝渗出和紧密连接蛋白表达在所有组中均无差异。HE染色显示载体组小鼠脑内有空泡性神经元变性,但疫苗接种组未观察到组织病变。载体组小鼠脑内TNF-α、IL-6和突触核蛋白上调,而疫苗接种组小鼠中这些因子受到抑制。IFN-β、IFN-γ、ISG15、Mx1和OAS1在疫苗接种组和载体组小鼠脑内无差异。此外,与载体组小鼠相比,疫苗接种组小鼠肠道内TNF-α和IL-6受到抑制,抗病毒因子增加。我们的研究表明,PRV XJ delgE/gI/TK可抑制PRV诱导的神经损伤以及肠道和脑内炎症,并激活肠道的先天免疫。