Abstract

Infection of Friend erythroleukemic (FL) cells by polyomavirus (Py) invariably results in the selection of persistently infected FL-Py cell lines and clones. Anti-Py serum treatment of FL-Py lines and clones leads to the loss of Py genome and consequent cell cure. Conversely, cure has not been obtained in FL-PytsA cell lines (isolated after infection by a Py thermosensitive early mutant) and their derivative clones cultivated for a long time at nonpermissive temperature (39 degrees C), where viral large-T protein is inactive. Rescue of viral particles has always been obtained after shifting cells to 32 degrees C. Integrated viral genomes were detected by blot hybridization in an FL-PytsA clone at 39 degrees C. Long-term observation of FL-Py cell lines and their derivative clones reveals a reciprocal selection mechanism (coevolution) between the viral and the cellular populations, resulting in either a completely virus-free Py-resistant FL cell line (cure) or in a continuously Py-shedding line bearing Py genome variants. Structural analysis of these viral populations has been carried out, and some viral variants have been isolated and characterized. On the basis of the results obtained, the possible mechanisms of Py persistence in FL cells will be discussed.

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