Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production

Abstract

Fischer rat fibroblasts, naturally resistant to killing by the fibrotropic strain of minute virus of mice [(parvovirus MVM(p)], became sensitive to MVM when transformed by polyomavirus. This sensitization did not involve an increase in the percentage of cells which synthesized viral capsid antigens or in the percentage of cells which produced infectious virus. The addition of anti-MVM antiserum to the growth medium of MVM-infected cells had only a small effect on their survival rates, indicating that the majority of the killing effect of MVM occurs in a single cycle of infection. The data indicate that cell killing by MVM is independent of infectious virus production and thus support the notion that the preferential cytolytic effect is affected by viral cytotoxic gene products which accumulate to intolerable levels in transformed cells but not in normal ones. Finally, using cells transformed with polyomavirus and genomic and subgenomic clones of polyomavirus, we showed that the extent of sensitization to killing by MVM depended on the transforming agent used.

Oncolytic Potential of Rodent Parvoviruses for Cancer Therapy in Humans: A Brief Review

“…It had been shown previously that autonomous parvovirus can induce cytotoxic effects in the absence of a complete replicative cycle (Cornelis et al, 1988a;Guetta et al, 1990;Rubio et al, 2001). Therefore, we investigated whether the toxicity of H-1 virus for malignant glioma cells was associated with viral replication and with the production of infectious H-1 particles.…”

Parvovirus H‐1 infection of human glioma cells leads to complete viral replication and efficient cell killing

“…Other studies showed that autonomous parvovirus can induce cytotoxic effects in the absence of a complete replicative cycle 26, 29, 36. This prompted us to investigate whether the pronounced toxicity of H‐1 virus for malignant glioma cells was associated with viral replication and with the production of infectious H‐1 virus particles.…”

“…Parvovirus H‐1 infection is known to inhibit the growth and jeopardize the survival of a number of in vitro ‐transformed or tumor‐derived human and rodent cell lines under conditions in which it does not lead to substantial cytocidal changes in untransformed cells 20, 25, 26, 27, 28, 29, 30. In laboratory animals, H‐1 virus is able to inhibit the formation or growth of tumors, and this oncosuppression is thought to result, at least in part, from virus‐induced oncolysis 20, 21, 46.…”

“…Autonomous parvoviruses were shown to preferentially kill in vitro transformed and tumor‐derived human and rodent cell lines, while limited‐to‐no cytocidal action was observed in nontransformed cells 25, 26, 27, 28, 29, 30. This selective oncolytic effect could also be seen in short‐term cultures of human breast and liver carcinoma cells vs. their corresponding normal counterparts 31, 32.…”

Inhibition of N‐methyl‐N′'‐nitro‐n‐nitrosoguanidine‐induced methotrexate and adriamycin resistance in CHO cells by adeno‐associated virus type 2

“…Instead, enhanced cell killing by AAV during drug selection of cells which survived MNNG treatment might result from viral cytotoxic gene products which may accumulate to intolerable levels, as shown for selective cell killing by autonomous parvoviruses (Rhode et al, 1987;Guetta et d., 1990). On the other hand, the elevated expression of the viral genome is not linked to virus production (Guetta et al, 1990). The much higher degree of selective killing of carcinogen-treated SV40transformed Chinese hamster cells (C063 1, C06O) by AAV in comparison to CHO-9 cells might be attributed to enhanced capacity to support AAV gene expression and full permissiveness for AAV multiplication in the SV40-transformed lines as well as to different kinetics of cytotoxicity by the carcinogens 7,12-dimethyl-benz[a]anthracene, 4-nitroquinoline-N-oxide, and benzo[a]pyrene used in those studies (Heilbronn et al, 1984).…”