title: N-Terminal Domain of Feline Calicivirus (FCV) Proteinase-Polymerase Contributes to the Inhibition of Host Cell Transcription.
abstract: Feline Calicivirus (FCV) infection results in the inhibition of host protein synthesis, known as "shut-off". However, the precise mechanism of shut-off remains unknown. Here, we found that the FCV strain 2280 proteinase-polymerase (PP) protein can suppress luciferase reporter gene expression driven by endogenous and exogenous promoters. Furthermore, we found that the N-terminal 263 aa of PP (PPN-263) determined its shut-off activity using the expression of truncated proteins. However, the same domain of the FCV strain F9 PP protein failed to inhibit gene expression. A comparison between strains 2280 and F9 indicated that Val27, Ala96 and Ala98 were key sites for the inhibition of host gene expression by strain 2280 PPN-263, and PPN-263 exhibited the ability to shut off host gene expression as long as it contained any two of the three amino acids. Because the N-terminus of the PP protein is required for its proteinase and shut-off activities, we investigated the ability of norovirus 3C-like proteins (3CLP) from the GII.4-1987 and -2012 isolates to interfere with host gene expression. The results showed that 3CLP from both isolates was able to shut off host gene expression, but 3CLP from GII.4-2012 had a stronger inhibitory activity than that from GII.4-1987. Finally, we found that 2280 PP and 3CLP significantly repressed reporter gene transcription but did not affect mRNA translation. Our results provide new insight into the mechanism of the FCV-mediated inhibition of host gene expression.
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. whx450650@163.com.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. 18745026359@163.com.|College of Veterinary Medicine, Northeast Agricultural University, Harbin 150001, China. 18745026359@163.com.
authors.forename: Shaopo
authors.initials: S
authors.lastname: Zu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. shellyfree@126.com.|College of Veterinary Medicine, Northeast Agricultural University, Harbin 150001, China. shellyfree@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. liuyongxiang0726@foxmail.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. tj6049345@126.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Nangang District, Harbin 150001, China. qld@hvri.ac.cn.
authors.forename: Liandong
authors.initials: L
authors.lastname: Qu
mesh_terms: D000818:Animals; D017927:Calicivirus, Feline / Q000472:pathogenicity*; D002460:Cell Line; D004252:DNA Mutational Analysis; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D010447:Peptide Hydrolases / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012321:DNA-Directed RNA Polymerases; D010447:Peptide Hydrolases
keywords: FCV; PP; inhibition; key function sites; transcription