title: The capsid proteins of Aleutian mink disease virus activate caspases and are specifically cleaved during infection.
abstract: Aleutian mink disease virus (AMDV) is currently the only known member of the genus Amdovirus in the family Parvoviridae. It is the etiological agent of Aleutian disease of mink. We have previously shown that a small protein with a molecular mass of approximately 26 kDa was present during AMDV infection and following transfection of capsid expression constructs (J. Qiu, F. Cheng, L. R. Burger, and D. Pintel, J. Virol. 80:654-662, 2006). In this study, we report that the capsid proteins were specifically cleaved at aspartic acid residue 420 (D420) during virus infection, resulting in the previously observed cleavage product. Mutation of a single amino acid residue at D420 abolished the specific cleavage. Expression of the capsid proteins alone in Crandell feline kidney (CrFK) cells reproduced the cleavage of the capsid proteins in virus infection. More importantly, capsid protein expression alone induced active caspases, of which caspase-10 was the most active. Active caspases, in turn, cleaved capsid proteins in vivo. Our results also showed that active caspase-7 specifically cleaved capsid proteins at D420 in vitro. These results suggest that viral capsid proteins alone induce caspase activation, resulting in cleavage of capsid proteins. We also provide evidence that AMDV mutants resistant to caspase-mediated capsid cleavage increased virus production approximately 3- to 5-fold in CrFK cells compared to that produced from the parent virus AMDV-G at 37 degrees C but not at 31.8 degrees C. Collectively, our results indicate that caspase activity plays multiple roles in AMDV infection and that cleavage of the capsid proteins might have a role in regulating persistent infection of AMDV.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, Mail Stop 3029, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.forename: Aaron Yun
authors.initials: AY
authors.lastname: Chen
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Best
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Bloom
authors.forename: David
authors.initials: D
authors.lastname: Pintel
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000453:Aleutian Mink Disease / Q000821:virology; D000454:Aleutian Mink Disease Virus / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008907:Mink / Q000821:virology*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature
chemical_list: D036022:Capsid Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D020169:Caspases