Novel Function of African Swine Fever Virus pE66L in Inhibition of Host Translation by the PKR/eIF2α Pathway
Zhou Shen, Chen Chen, Yilin Yang, Zhenhua Xie, Qingying Ao, Lu Lv, Shoufeng Zhang, Huanchun Chen, Rongliang Hu, Hongjun Chen, Guiqing Peng
Abstract
African swine fever virus (ASFV) is a member of the nucleocytoplasmic large DNA virus superfamily that predominantly replicates in the cytoplasm of infected cells. The ASFV double-stranded DNA genome varies in length from approximately 170 to 193 kbp depending on the isolate and contains between 150 and 167 open reading frames (ORFs), of which half the encoded proteins have not been explored. Our study showed that 14 proteins had an obvious inhibitory effect on Renilla luciferase (Rluc) gene synthesis, with pE66L showing the most significant effect. Furthermore, the transmembrane (TM) domain of pE66L broadly inhibited host protein synthesis in a PKR/eIF2a pathway-dependent manner. Loss of pE66L during ASFV infection had little effect on virus replication, but significantly recovered host protein synthetic. Based on the above results, our findings expand our view of ASFV in determining the fate of host-pathogen interactions.