ANTINEOPLASIC ACTIVITY OF PARVOVIRUSES

The family of Parvoviridae is composed of small, nuclear-replicating viruses that are without envelope and contain an essentially single-stranded, linear DNA genome. Certain parvoviruses proved to have the remarkable capacity to prevent the formation of spontaneous as well as virally- and chemically-induced tumors in laboratory animals. Established tumor cells serve as targets for the antineoplasic activity of parvoviruses, since the growth of preformed cancer cells transplanted in recipient animals can also be inhibited by these viruses. Furthermore, epidemiological studies in humans have revealed a correlation between serological evidence of parvoviral infection and a lower incidence of certain cancers. The parvoviral life-cycle appears to depend on cellular factors that are expressed as a function of proliferation and differentiation. This subordination may account for the oncotropism of parvoviruses in vivo and for the specificity of their interactions with (pre-)neoplasic cells under appropriate culture conditions. Thus, certain parvoviruses were found to preferentially lyse initiated or stably transformed cells in vitro, as a possible result of the stimulation of the production and/or activity of cytotoxic viral proteins. Parvoviruses can also have a cytostatic effect and cause the reversion of transformation traits, parallel to the down-modulation of the expression of defined genes, in particular oncogenes. Such direct disturbance of neoplasic cells or their precursors may participate in the oncosuppressive activity of parvoviruses, although indirect viral effects mediated by host defense mechanisms also deserve to be considered. Altogether, these properties suggest the possible use of parvoviruses as probes to investigate the process of malignant transformation. Further research is needed to determine whether infections with parvoviruses may find a place in the prevention and treatment of human cancers.