Chaperoning the Driver of Filovirus Egress to a Dead End

Autophagy. 2023 Feb 10. doi: 10.1080/15548627.2023.2178781. Online ahead of print.ABSTRACTEbola virus (EBOV) and Marburg virus (MARV) are zoonotic, virulent pathogens that cause sporadic and global outbreaks of severe hemorrhagic fever. Re-emergence of these filoviruses remains a global public health threat, highlighting the need for novel countermeasures to control and treat future disease outbreaks. The EBOV VP40 matrix protein drives virion assembly and egress. We recently reported that BAG3 and HSPA/HSP70, two central components of chaperone-assisted selective autophagy (CASA), target VP40 for autophagic sequestration and degradation, thereby inhibiting virus egress and spread. In addition, we found that expression of the EBOV glycoprotein (GP) activates MTORC1, the gateway regulator of autophagy. Notably, pharmacological suppression of MTORC1 signaling by rapamycin activates autophagy and blocks filovirus egress. These findings highlight the MTORC1-CASA axis as a regulator of filovirus egress and suggest new opportunities for antiviral development and intervention.PMID:36763514 | DOI:10.1080/15548627.2023.2178781

Source: Autophagy - February 10, 2023 Category: Cytology Authors: Jingjing Liang Marija A Djurkovic Olena Shtanko Ronald N Harty Source Type: research