Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity.

Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity. Autophagy. 2019 Jul 18;:1-20 Authors: Yang B, Xue Q, Guo J, Wang X, Zhang Y, Guo K, Li W, Chen S, Xue T, Qi X, Wang J Abstract Macroautophagy/autophagy is an essential cellular response in the fight against intracellular pathogens. Although some viruses can escape from or utilize autophagy to ensure their own replication, the responses of autophagy pathways to viral invasion remain poorly documented. Here, we show that peste des petits ruminants virus (PPRV) infection induces successive autophagic signalling in host cells via distinct and uncoupled molecular pathways. Immediately upon invasion, PPRV induced a first transient wave of autophagy via a mechanism involving the cellular pathogen receptor NECTIN4 and an AKT-MTOR-dependent pathway. Autophagic detection showed that early PPRV infection not only increased the amounts of autophagosomes and LC3-II but also downregulated the phosphorylation of AKT-MTOR. Subsequently, we found that the binding of viral protein H to NECTIN4 ultimately induced a wave of autophagy and inactivated the AKT-MTOR pathway, which is a critical step for the control of infection. Soon after infection, new autophagic signalling was initiated that required viral replication and protein expression. Interestingly, expression of IRGM and HSPA1A was significantly upregulated foll...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research