Typical gene expression profile of pseudorabies virus reactivation from latency in swine trigeminal ganglion

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Typical gene expression profile of pseudorabies virus reactivation from latency in swine trigeminal ganglion Hai-Hua Wang 1,2 & Jie Liu 1 & Lin-Tao Li 1 & Huan-Chun Chen 1 & Wan-Po Zhang 3 & Zheng-Fei Liu 1 Received: 2 December 2019 / Revised: 15 April 2020 / Accepted: 4 June 2020 # Journal of NeuroVirology, Inc. 2020

Abstract Pseudorabies virus (PRV) establishes a lifelong latent infection in swine trigeminal ganglion (TG) following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Muscle injection combined with intravenous deliver of the synthetic corticosteroid dexamethasone (DEX) consistently induces reactivation from latency in pigs. In this study, PRV-free piglets were infected with PRV. Viral shedding in nasal and ocular swabs demonstrated that PRV infection entered the latent period. The anti-PRV antibody was detected by enzyme-linked immunosorbent assay and the serum neutralization test, which suggested that the PRV could establish latent infection in the presence of humoral immunity. Immunohistochemistry and viral genome detection of TG neurons suggested that PRV was reactivated from latency. Viral gene expressions of IE180, EP0, VP16, and LLT-intron were readily detected at 3-h post-DEX treatment, but gB, a γ1 gene, was not detectable. The differentially expressed phosphorylated proteins of TG neurons were analyzed by ITRAQ coupled with LC-MS/ MS, and p-EIF2S2 differentially expression was confirmed by western blot assay. Taken together, our study provides the evidence that typical gene expression in PRV reactivation from latency in TG is disordered compared with known lytic infection in epithelial cells. Keywords Pseudorabies virus . Trigeminal ganglion . Latency . Reactivation

Introduction Pseudorabies virus (PRV), an important member of the alpha herpesvirus subfamily, causes Aujeszky’s disease in swine. It results in reproductive, neurological, and respiratory diseases in the pig industry worldwide (Muller et al. 2011; Pomeranz et al. 2005). Alphaherpesvirus infection starts in epithelial cells of nasal throat and eyes and spreads in the retrograde

* Wan-Po Zhang [email protected] * Zheng-Fei Liu [email protected] 1

State Key Laboratory of Agricultural Microbiology and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China

2

Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China

3

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China

direction to the peripheral nervous system (PNS) during primary infection, while virus was released in the anterograde direction from infected PNS neurons to peripheral epithelial cells after reactivation (Engel et al. 2015). Following acute infection, PRV establishes a lifelong latency in the sensory ganglia, e.g., the trigeminal ganglion (TG), in natural hosts. Vaccination has been shown to reduce clinical signs rather than clear laten