title: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection.
abstract: Although H-1 parvovirus is used as an antitumor agent, not much is known about the relationship between its specific tropism and oncolytic activity. We hypothesize that VP2, a major capsid protein of H-1 virus, determines H-1-specific tropism. To assess this, we constructed chimeric H-1 viruses expressing Kilham rat virus (KRV) capsid proteins, in their complete or partial forms. Chimeric H-1 viruses (CH1, CH2 and CH3) containing the whole KRV VP2 domain could not induce cytolysis in HeLa, A549 and Panc-1 cells. However, the other chimeric H-1 viruses (CH4 and CH5) expressing a partial KRV VP2 domain induced cytolysis. Additionally, the significant cytopathic effect caused by CH4 and CH5 infection in HeLa cells resulted from preferential viral amplification via DNA replication, RNA transcription and protein synthesis. Modeling of VP2 capsid protein showed that two variable regions (VRs) (VR0 and VR2) of H-1 VP2 protein protrude outward, because of the insertion of extra amino-acid residues, as compared with those of KRV VP2 protein. This might explain the precedence of H-1 VP2 protein over KRV in determining oncolytic activity in human cancer cells. Taking these results together, we propose that the VP2 protein of oncolytic H-1 parvovirus determines its specific tropism in human cancer cells.
authors: BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea.
authors: I-R
authors: IR
authors: Cho
authors: BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea.
authors: S
authors: S
authors: Kaowinn
authors: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: J
authors: J
authors: Song
authors: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: S
authors: S
authors: Kim
authors: Department of Biological Sciences, Dong-A University, Busan, Republic of Korea.
authors: S S
authors: SS
authors: Koh
authors: Department of Microbiology, Pusan National University, Busan, Republic of Korea.
authors: H-Y
authors: HY
authors: Kang
authors: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors: N-C
authors: NC
authors: Ha
authors: Department of Microbiology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors: K H
authors: KH
authors: Lee
authors: College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors: H-S
authors: HS
authors: Jun
authors: BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea.
authors: Y-H
authors: YH
authors: Chung
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D052661:H-1 parvovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods; D010322:Parvoviridae Infections / Q000821:virology*; D051381:Rats; D014162:Transfection
chemical_list: D036022:Capsid Proteins