Hippo signaling pathway regulates Ebola virus transcription and egress
Year: 2024
Type: article
Abstract: Filovirus-host interactions play important roles in all stages of the virus lifecycle. Here, we identify LATS1/2 kinases and YAP, key components of the Hippo pathway, as critical regulators of EBOV transcription and egress. Specifically, we find that when YAP is phosphorylated by LATS1/2, it localizes to the cytoplasm (Hippo “ON”) where it sequesters VP40 to prevent egress. In contrast, when the Hippo pathway is “OFF”, unphosphorylated YAP translocates to the nucleus where it transcriptionally activates host genes and promotes viral egress. Our data reveal that LATS2 indirectly modulates filoviral VP40-mediated egress through phosphorylation of AMOTp130, a positive regulator of viral egress, but more surprisingly that LATS1/2 kinases directly modulate EBOV transcription by phosphorylating VP30, an essential regulator of viral transcription. In sum, our findings highlight the potential to exploit the Hippo pathway/filovirus axis for the development of host-oriented countermeasures targeting EBOV and related filoviruses. Here, the authors identify the host proteins LATS1/2 and YAP of the Hippo pathway to regulate Ebola virus transcription and virus production/egress. They show that YAP activity is important for virus particle production and release, while LATS1/2 are critical for EBOV mRNA synthesis and viral protein expression.
Source: Nature Communications
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: Dueling PPxY Motifs of Filovirus VP40 and Host Angiomotin: Effects on Innate Immune Defenses and Tight Junction Integrity at Immune Privileged Sites, Modular Domains of Host Proteins Regulate Filovirus Maturation, G2817431447, The role of macrophage podosomes in Ebola virus pathogenesis, G4286515554, G4542888288, Tunneling nanotubes as an alternate route of Ebola virus dissemination, Role of Host Angiomotin as a Central Regulator of Filovirus Egress and Dissemination, G5569963067, G5635430333, G5832342026, G6547220531, G6690028980, G7092970984, G7296076320, G8215176960, G8312506762, G8563393162, G9000144582, G9000175090
OpenAlex ID: W4401534106