Interaction of K papovavirus with hamster cells: transformation of glial cells in vitro but failure of the virus to produce central nervous system tumors in vivo.

Primary cultures of lungs, kidneys, and glial cells derived from midgestation Syrian hamsters were inoculated with 10(5) hemagglutinating units of murine K-papovavirus and were serially subcultivated to allow appearance of lines of persistently infected or transformed cells. K virus did not replicate in renal cell cultures and produced only transient productive infection of lung cells. Evidence of K virus-induced cell transformation was not detected in either of these cultures. Inoculation of glial cultures with K virus, however, resulted initially in a protracted infection in which 80--100 percent of cells expressed K virus V antigen for 18 subcultivations and in which cloning experiments suggested that all cells in the culture contained the viral genome. After 18 subcultivations numbers of positive cells rapidly diminished, and cells appeared which exhibited altered morphology and density dependence. These altered cells (KVHG3 cells) grew well in serum-free media, could be cloned in soft agar, and were negative for infectious virus or K virus V antigen. Although KVHG3 cells did not exhibit staining when reacted with antisera to K virus T antigen, Southern blot analysis of these cultures demonstrated the presence of K virus DNA integrated into the host chromosomal DNA and indicated that some rearrangement of the viral genome had occurred. Attempts to produce tumors in hamsters with these cells were unsuccessful, as were attempts to induce tumors in newborn hamsters by intracranial inoculation of K virus. The present study demonstrates that K virus is capable of causing productive infection and cell transformation in primary cultures of fetal hamster glial cells but that other hamster cell types are relatively resistant to the virus and that both K virus and K virus-transformed hamster cells are poorly oncogenic for hamsters in vivo.