1.A.149.1.3
ORF3 of 114 aas and 1 TMS.  It is a small multifunctional phosphoprotein involved in virion morphogenesis, egress and counteracting host innate immunity. It plays critical roles in the final steps of viral release by interacting with host TSG101, a member of the vacuolar protein-sorting pathway and using other cellular host proteins involved in the vesicle formation pathway. It also acts as a viroporin and forms ion conductive pores allowing viral particle release (Ding et al. 2017). It impairs the generation of type I interferon by down-regulating host TLR3 and TLR7 as well as their downstream signaling pathways.  It down-regulates the phosphorylation of host IRF3 via the interaction with host SIRP-alpha, thereby inhibiting IFN-I expression. pORF3 plays a pivotal role in inducing Beclin1-mediated autophagy that helps HEV-1 replication as well as its exit from cells (Srivastava et al. 2023).