Rab5c promotes RSV and ADV replication by autophagy in respiratory epithelial cells.

Respiratory system diseases caused by respiratory viruses are common and exert tremendous pressure on global healthcare system. In our previous studies, we found that Long non-coding RNA NRAV (Lnc NRAV) and its target molecule Rab5c plays a significant role in respiratory virus infection. However, the mechanism by which Rab5c affects virus replication remains unclear. Rab5c, a protein mainly localized on the cell membranes and in early endosomes and phagosomes, participates in endocytosis mediated by clathrin and regulates the fusion of early endosome, maturation of early phagosomes, and autophagy. Therefore, we inferred that Rab5c impacts virus replication, which might be related to endocytosis or autophagy. We selected RSV (respiratory syncytial virus) as a representative enveloped virus and ADV (Adenovirus) as a representative non-enveloped virus to explore the possible mechanism of RSV and ADV replication promoted by Rab5c in A549 cells and in Rab5c-overexpressing mice. Here, we confirmed that the activated Rab5c promotes RSV and ADV replication and the inactivated Rab5c inhibits their replication. However, Rab5c promoting RSV and ADV replication is not mediated by endocytosis rather by autophagy in respiratory epithelial cells. Our study showed that Rab5c upregulates LC3-Ⅱ (microtubule-associated protein 1 light chain 3 beta) protein expression levels by interacting with Beclin1, a key autophagy molecule, which can induce autophagy and promote replication of ADV and RSV. This study enriches the understanding of the interaction between respiratory viruses and Rab5c, providing new insights for virus prevention and treatment.