Enterovirus 3A protein disrupts endoplasmic reticulum homeostasis through interaction with GBF1

Enterovirus A71 (EV-A71) is a single-stranded, positive sense RNA virus causing endoplasmic reticulum stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). The 3A protein of EV-A71 was identified as a major regulator of the UPR caused by infection with EV-A71. To identify the molecular pathways for the 3A protein to regulate the UPR, we performed RNA sequencing (RNA-seq) with RD cells expressing the 3A protein. Wild type or defective mutant of 3A protein that carried alanine substitutions of Ile8 or Ile10 (3A-I8A or -I10A) was expressed in the cells. The RNA-seq with cells expressing either WT or mutant 3A was performed. Overall design: To investigate the functions of EV-A71 3A protein, we generated a defective mutant of 3A protein that carried alanine substitutions of Ile8 or Ile10 (3A-I8A or -I10A). Gene expression profiling analysis of RD cells, RD cells expressing wild type 3A protein, RD cells expressing 3A-I8A, or RD cells expressing 3A-I10A was performed.