The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection

Fung, To Sing; Torres, Jaume; Liu, Ding Xiang

Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.