Progranulin-driven lysosomal acidification facilitates exocytosis of PHEV-hijacked lysosomes for viral release.

ABSTRACT: Porcine hemagglutinating encephalomyelitis virus (PHEV) hijacks lysosomes, repurposing them as vehicles for viral release by disrupting their function. Progranulin (PGRN), a lysosomal glycoprotein essential for lysosomal regulation, plays a pivotal role in this process. This study demonstrates that PHEV infection reduces full-length PGRN levels while enhancing its lysosomal targeting. Notably, PGRN knockout mice exhibit resistance to PHEV infection, implicating PGRN in PHEV-induced lysosomal dysfunction and viral release. Mechanistically, PHEV infection-induced enhancement of PGRN lysosomal trafficking depends on the concurrent harnessing of two distinct pathways for lysosomal delivery of PGRN. This enhanced targeting involves increased vacuolar-type ATPase recruitment, intensifying lysoso

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12802303 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature