Lamtor5 interacts with LMBV PCNA to promote viral replication through autophagy.

Abstract

Lamtor5, a subunit of the target of the Ragulator-mediated mechanism in response to amino acid-activated rapamycin complex 1 (mTORC1), plays an important role in the mTOR signalling pathway and can influence viral replication and host cell antiviral status by regulating cell growth and metabolism. Therefore, as a member of the Ragulator complex, Lamtor5 plays a crucial role in viral infection. However, the role of Lamtor5 in ranavirus infection has not been reported. In this study, we investigated the function of epithelioma papulosum cyprini (EPC) Lamtor5 in the replication of largemouth bass virus (LMBV). In this study, we found that EPC Lamtor5 promoted viral replication and interacted with LMBV proliferating cell nuclear antigen (PCNA), as confirmed by co-immunoprecipitation (co-IP), GST pull-down, and immunofluorescence. Furthermore, both Lamtor5 and LMBV PCNA induced autophagy in EPC cells, and starvation- or rapamycin-induced autophagy significantly increased viral replication, whereas the inhibition of autophagic flux by CQ suppressed viral growth. Therefore, we propose that EPC Lamtor5 is a proviral factor and that it and LMBV PCNA promote viral replication by inducing autophagy in EPC cells. Regarding the mechanism by which LMBV PCNA promotes autophagy, we speculate that the interaction between PCNA and Lamtor5 changes the structure of the Ragulator complex, which regulates downstream mTORC1 activity, thus causing changes in autophagy.