It is considered a source of precursor membranes for viral replication complex formation.40, 41, 42 In addition, our previous study showed that viral 2C protein interacts with the host ER transmembrane protein reticulon 3 and is required for EV71 replication.26 Recently, the ER-derived autophagosome-like vesicle that participates in nonlytic viral spread and virus infection has emerged as a topic in picornavirus studies.43, 44 Therefore, learning how viruses modulate the ER membrane or ER proteins may provide new insights for the antiviral research. This evidence concerns the gene RTN3 and viral infectious disease.