title: Porcine epidemic diarrhea virus induces caspase-independent apoptosis through activation of mitochondrial apoptosis-inducing factor.
abstract: The present study sought to investigate whether porcine epidemic diarrhea virus (PEDV) induces apoptosis and to elucidate the mechanisms associated with apoptotic cell death after PEDV infection. PEDV-infected cells showed evidence of apoptosis in vitro and in vivo. However, experimental data indicated that the caspase cascade is not involved in PEDV-induced apoptotic cell death. Interestingly, mitochondrial apoptosis-inducing factor (AIF) was found to translocate to the nucleus during PEDV infection, and AIF relocalization was completely abrogated by the presence of cyclosporin A (CsA), an inhibitor of cyclophilin D (CypD) that is an essential component of the mitochondrial permeabilization transition pore (mPTP) complex. CsA treatment resulted in significant inhibition of PEDV-triggered apoptosis and suppressed PEDV replication. Furthermore, direct inhibition of AIF strongly impaired PEDV infection and virus-induced apoptosis. Altogether, our results indicate that a caspase-independent mitochondrial AIF-mediated pathway plays a central role in PEDV-induced apoptosis to facilitate viral replication and pathogenesis.
authors.affiliation: Animal Virology Laboratory, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Animal Virology Laboratory, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: changhee@knu.ac.kr.
authors.forename: Changhee
authors.initials: C
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D018352:Coronavirus Infections / Q000201:enzymology / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053485:Porcine epidemic diarrhea virus / Q000235:genetics / Q000502:physiology*; D013552:Swine; D013553:Swine Diseases / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D014779:Virus Replication
chemical_list: D051033:Apoptosis Inducing Factor; D000081406:Peptidyl-Prolyl Isomerase F; D020169:Caspases; D021983:Cyclophilins
keywords: Apoptosis-inducing factor; Apoptotic cell death; Caspase-independent; PEDV; Pathogenesis