Hippo signaling pathway regulates Ebola virus transcription and egress

Ebola (EBOV) virus is an emerging pathogen of the Filoviridae family that causes sporadic and global outbreaks of acute hemorrhagic fever in humans, resulting in mortality rates as high as 90%. Filoviruses can establish chronic/persistent infections in immunologically privileged sites and their re-emergence can cause long-term sequelae or death. Identifying and characterizing filovirus-host interactions that impact the virus lifecycle can be exploited as potential targets for developing host-oriented countermeasures and represent a potential way forward. This research reveals how key effector YAP and core kinases LATS1/2 of the Hippo pathway intersect with the EBOV lifecycle. Hippo signaling-regulated YAP localization and activity shape the cellular environment towards one that either inhibits (Hippo ON) or promotes (Hippo OFF) viral egress. LATS2 indirectly regulates egress by phosphorylating AMOTp130; whereas, LATS1/2 kinases directly regulate EBOV transcription by interacting with EBOV NP and phosphorylating EBOV VP30. This research provides mechanistic insights into the diverse Hippo pathway-mediated control of several stages of the EBOV lifecycle, potentially leading to identifying and exploiting antiviral targets for building host-oriented countermeasures against EBOV and similar infections.
(DKW)