RETRACTED ARTICLE: VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection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

Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction

“…Studies in two different tumor models have correlated this LuIII phenotype to VP2 [ 7 , 24 , 25 ]. Studies of H-1PV and other rodent protoparvoviruses also support a tumor tropism determinant within this protein [ 26 ]. VP2 forms virus-like-particles (VLPs) for members of the protoparvoviruses that are otherwise antigenically and structurally equivalent to VP1/2/3 genome packaging capsids [ 27 , 28 , 29 ].…”

Possible risks posed by single‐stranded DNA viruses of pigs associated with xenotransplantation

“…Similarly, the rodent H1 parvovirus is well studied for its oncolytic potential in human cancer cells . The ability of the H1 virus to selectively infect human cancer cells is thought to be determined by the capsid protein and enabled by the increased rate of proliferation of the cancerous cells and their subdued antiviral mechanisms . In the case of oncolytic rodent H1 parvovirus, its ability to replicate in human cells is proof of having sufficient factors for the virus to replicate and produce an infective progeny H1 virus in cancerous cells.…”