title: Ceramide formation mediated by acid sphingomyelinase facilitates endosomal escape of caliciviruses.
abstract: Our recent results demonstrated that bile acids facilitate virus escape from the endosomes into the cytoplasm for successful replication of porcine enteric calicivirus (PEC). We report a novel finding that bile acids can be substituted by cold treatment for endosomal escape and virus replication. This endosomal escape by cold treatment or bile acids is associated with ceramide formation by acid sphingomyelinase (ASM). ASM catalyzes hydrolysis of sphingomyelin into ceramide, which is known to destabilize lipid bilayer. Treatment of LLC-PK cells with bile acids or cold led to ceramide formation, and small molecule antagonists or siRNA of ASM blocked ceramide formation in the endosomes and significantly reduced PEC replication. Inhibition of ASM resulted in the retention of PEC, feline calicivirus or murine norovirus in the endosomes in correlation with reduced viral replication. These results suggest the importance of viral escape from the endosomes for the replication of various caliciviruses.
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Vinay
authors.initials: V
authors.lastname: Shivanna
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. Electronic address: kchang@vet.ksu.edu.
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Chang
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002139:Caliciviridae / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002415:Cats; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism*; D003080:Cold Temperature; D011992:Endosomes / Q000201:enzymology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects / Q000821:virology; D051379:Mice; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013552:Swine; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D001647:Bile Acids and Salts; D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase
keywords: Acid sphingomyelinase; Caliciviruses; Ceramide formation; Endosomal escape; Replication