BIPHASIC STIMULATION OF POLYAMINE BIOSYNTHESIS IN PRIMARY MOUSE KIDNEY CELLS BY INFECTION WITH POLYOMA-VIRUS - UNCOUPLING FROM DNA AND RIBOSOMAL-RNA SYNTHESIS

Infection of primary cultures of mouse kidney cells with polyoma virus causes a biphasic increase in the activities of L-ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (SAMD; S-adenosyl-L-methionine carboxy-lyase; EC 4.1.1.50), and in the level of the polyamines putrescine, spermidine and spermine. An early peak occurs during the period when early viral mRNA is synthesized and prior to the onset of virus-induced synthesis of host cell DNA. A late peak coincides in time with the maximum rate of virus-induced synthesis of cellular DNA. A similar biphasic stimulation of polyamine synthesis is induced even when DNA synthesis is prevented by 5-fluorodeoxyuridine. Actinomycin D (AMD) in a dose that inhibits rRNA synthesis causes no inhibition of ODC or SAMD. In a dose that inhibits mRNA synthesis as well, short-term AMD treatment causes superinduction of ODC but inhibition of SAMD. Prolonged treatment with the high dose of AMD inhibits ODC, indicating that late ODC activity may be dependent on mRNA synthesized during early infection. Cycloheximide effectively obliterates the ODC and SAMD activities during the entire infectious cycle. Uncoupling from DNA and rRNA synthesis suggests that polyamine synthesis is regulated independently of these events. The formation of ODC may be subject to post-transcriptional control, whereas that of SAMD may be regulated primarily at the transcriptional level. [These findings may have relevance to neoplastic cell proliferation.].