Ren Li , Zhiwei Pan , Jialin Wu , Shuai Yue , Yao Lin , Yang Yang , Zhirong Li , Li Hu , Jianfang Tang , Lingling Shan , Qin Tian , Peng Jiang , Ping Wei , Lilin Ye , Pinghuang Liu , Xiangyu Chen
J Virol.2020 Sep 30;JVI.01627-20.doi: 10.1128/JVI.01627-20. Online ahead of print.
Protection of a majority of viral vaccines is mediated by CD4 T cell-dependent humoral immunity. The methyltransferase enhancer of zeste homolog 2 (EZH2) dictates the differentiation of naïve CD4 T cells into distinct effector T helper subsets at the onset of acute viral infection. However, whether and how EZH2 manipulates differentiated virus-specific CD4 T cell expansion remains to be elucidated. Here, we found EZH2 is integral for virus-specific CD4 T cell expansion in a mouse model of acute viral infection. By a mechanism that involves fine-tuning the mechanistic target of rapamycin (mTOR) signaling, EZH2 participates in integrating metabolic pathways to support cell expansion. The genetic ablation of EZH2 leads to impaired cellular metabolism and consequent poor CD4 T cell response to acute viral infection. Thus, we identified EZH2 as a novel regulator in virus-specific CD4 T cell expansion during acute viral infection.IMPORTANCECD4 T cell response is critical in curtailing viral infection or eliciting efficacious viral vaccination. Highly efficient expansion of virus-specific CD4 T cells culminates qualified CD4 T cell response. Here, we found that the epigenetic regulator EZH2 is prerequisite for virus-specific CD4 T cell response, with a mechanism coupling of cell expansion and metabolism. Thus, our study provides valuable insights for strategies targeting EZH2 to improve efficacy of CD4 T cell-based viral vaccine and to help treat diseases associated with aberrant CD4 T cell response.
Copyright © 2020 Li et al.