Lu Cui,Xuefeng Li,Zheyi Liu,Xiaoxiao Liu,Yongxin Zhu,Yu Zhang, Zongxi Han,Yilei Zhang,Shengwang Liu,Hai Li

Virology.2024 Jun 26:597:110159.doi: 10.1016/j.virol.2024.110159. Online ahead of print.

Abstract

Therapies targeting virus-host interactions are seen as promising strategies for treating gallid alphaherpesvirus 1 (ILTV) infection. Our study revealed a biphasic activation of two MAPK cascade pathways, MEK/ERK and p38 MAPK, as a notably activated host molecular event in response to ILTV infection. It exhibits antiviral functions at different stages of infection. Initially, the MEK/ERK pathway is activated upon viral invasion, leading to a broad suppression of metabolic pathways crucial for ILTV replication, thereby inhibiting viral replication from the early stage of ILTV infection. As the viral replication progresses, the p38 MAPK pathway activates its downstream transcription factor, STAT1, further hindering viral replication. Interestingly, ILTV overcomes this biphasic antiviral barrier by hijacking host p38-AKT axis, which protects infected cells from the apoptosis induced by infection and establishes an intracellular equilibrium conducive to extensive ILTV replication. These insights could provide potential therapeutic targets for ILTV infection.

Keywords: Apoptosis; Cell metabolism; Extracellular signal‐regulated kinase (ERK); Herpesvirus; Mitogen‐activated protein kinase (MAPK); p38 MAPK.