VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

• Published in: Cancer gene therapy Vol. 22; no. 5; pp. 271 - 277
• Main Authors: Cho, I-R, Kaowinn, S, Song, J, Kim, S, Koh, S S, Kang, H-Y, Ha, N-C, Lee, K H, Jun, H-S, Chung, Y-H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2015
• Subjects: Animals; Cancer; Cancer cells; Capsid Proteins - genetics; Capsid Proteins - metabolism; Care and treatment; Chemotherapy; Genetic aspects; H-1 parvovirus - genetics; H-1 parvovirus - metabolism; H-1 parvovirus - physiology; H-1 virus; Health aspects; HeLa Cells; Humans; Kilham rat virus; Neoplasms - genetics; Neoplasms - therapy; Neoplasms - virology; Oncology, Experimental; Oncolytic Virotherapy - methods; Parvoviridae Infections - virology; Parvovirus; Parvoviruses; Rats; Transfection; Viral proteins; United States; South Korea
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/cgt.2015.17

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.