Stability of vaccinia virus DNA during persistent infections: accumulation of left-end deletions and of tandem repeats at both ends of the viral genome and prevention by interferon.

The stability of the large vaccinia virus genome (122 MDa) has been studied in long-term cultures of persistently infected Friend erythroleukemia (FEL) cells. Deletions of about 8 MDa at the left terminus of vaccinia DNA are generated at early passages, and are maintained even after 2 years of continuous cell passages. The generation of deletions is followed by a stable accumulation of tandem repeats up to 6 MDa at the left end and up to 2 MDa at the right end of vaccinia DNA. Neither translocations nor rearrangements of DNA are observed during persistent infection. A recombinational mechanism within the tandem repeats or a mechanism similar to that described for adenovirus might explain the reiteration of tandem repeats at both ends. Significantly, in persistently infected cultures continuously treated with interferon (IFN) both the deletion and the large accumulation of tandem repeats were completely blocked. We suggest that reiteration of tandem repeats at the termini of vaccinia DNA might provide signals for more efficient virus multiplication in FEL cells.