Is ribonucleotide reductase the transforming function of herpes simplex virus 2?

Abstract

Transformation of cells by herpes simplex virus 2 (HSV-2) can be induced by the BglII C (0.43–0.58 map units) or N (0.58–0.625) fragments of the viral genome1–3. Sequences partially overlapping both fragments (0.566–0.602) encode two 3′ co-terminal mRNAs4–6; these in turn direct the synthesis of two related polypeptides of molecular weight 140,000 (140K) and 35K (refs 4,7), which may be involved in transformation7. Recently, a temperature-sensitive (ts) mutation affecting HSV-induced ribonucleotide reductase has been mapped within this common region (B. M. Dutia, personal communication). We have partially purified the induced reductase and raised a rabbit antiserum to it which inhibits the enzyme activity and immunoprecipitates from infected cells a 144K polypeptide and minor species including a 38K polypeptide8. Here we show that a monoclonal antibody to the putative transforming proteins7 competes with the rabbit serum for the 144K and 38K antigens and also immunoprecipitates specifically the induced reductase activity. These results suggest a possible role for ribonucleotide reductase in HSV-2-induced transformation.