RNA synthesis specific for an integrated adenovirus genome during the cell cycle

Abstract

WHEN adenovirus transforms a cultured mammalian cell, substantial portions of the viral genome can be integrated into the host cell chromosomes and at least a fraction of this integrated genome is transcribed¹. Approximately 50% of the early sequences observed in the lytic infections are synthesised in the transformed cell². In randomly growing transformed rat embryo cells, the virus transcripts in the nucleus are in the large molecular weight, heterogeneous RNA covalently linked to cellular RNA³. These transcripts are apparently processed before they appear on cytoplasmic polyribosomes³. To date, there has been little evidence concerning the synthesis and post-transcriptional modifications of viral transcripts during the cell cycle in the transformed cells. The first question to be asked is, is there continuous synthesis of viral transcripts from at least some portion of the integrated genome, or is synthesis limited to one phase of the cell cycle? We have investigated this question in synchronised rat embryo cells transformed with adenovirus type 2 (Ad2-T)⁴. The synthesis of viral RNA transcripts was correlated with the life cycle of the cell which can be defined as consisting of a period of DNA synthesis (S phase) followed by a period of growth before mitosis (G₂), mitosis (M), and another growth period following division prior to DNA synthesis (G₁). Our data indicate that virus-specific RNA was transcribed throughout the cell cycle along with cellular RNA synthesis. Viral RNA transcription was restricted during mitosis coincident with the restriction of cellular RNA synthesis.