Regulatory effects of persistent measles virus infection on tumorigenicity and protooncogene expression in neuroblastoma cells.

MS is among the infectious agents known to persistently infect cells of the CNS. Clones NS20/Y and NS20/MS persistently infected with MS, both originating from the C1300 mouse neuroblastoma, were used. Multiple effects of the MS infection on the neuronal cell communication, expression of protooncogenes tumorigenicity and on the presence of immunoregulatory molecules were studied. Our results demonstrate that the level of the MHC class I and II antigens and beta-2 microglobulin was elevated in the MS infected cells. Furthermore, MS infection results in the significant increase of protein kinase C (PKC) activity concomitantly with the elevation of PKC-I specific m-RNA. The MS infection was found to affect also the expression of the protooncogenes known to associate with the PKC signaling system. Thus, the level of c-fos mRNA was elevated in the MS infected cells, while there were almost no changes in the c-myc gene expression. Ki-ras and Ha-ras appeared to be regulated differently by MS infection. The level of Ki-ras mRNA was unchanged, but the expression of the Ha-ras gene was markedly depressed, correlating well with the low tumorigenicity of the MS infected neuroblastoma cells in nude mice. Our results suggest that viral infection may be beneficial in certain cases of depressing oncogenic genes which may contribute to the development and maintenance of the malignant phenotype.