Synthesis of type‐C virus particles from murine cultured cells induced by iododeoxyuridine. VI. Biosynthesis of reverse transcriptase

Treatment with 5‐iodo‐2'‐deoxyuridine (IdUrd) of BALB/3T3 cells non‐productively transformed with Kirsten murine sarcoma virus (K‐BALB) results in the induction of extracellular type‐C virus production with a concomitant appearance of intracellular reverse transcriptase. Production of BALB virus‐2 (v‐2) and its Kirsten sarcoma virus pseudo‐type, occurring 2‐3 days after IdUrd treatment, is inhibited and stimulated by interferon and dexamethasone, respectively, By contrast, and as previously reported, neither compound affects synthesis of N‐tropic virus (BALB virus‐1) which is produced later (5‐7 days) after IdUrd treatment. The stimulatory and inhibitory activities of these compounds are partially antagonistic since: (1) the simultaneous presence of both dexamethasone and interferon results in a virus production level between those observed with either compound alone; and (2) increasing the dexamethasone concentration at a fixed interferon concentration increases virus production. However, the effects of these two compounds on the appearance of an intracellular viral protein (reverse transcriptase) after IdUrd treatment were unexpected. The post‐induction appearance of intracellular reverse transcriptase is inhibited by interferon but is not affected by dexamethasone. This suggests that dexamethasone stimulates a step after protein synthesis, and that interferon inhibits an earlier step (translational or pre‐translational) or that it enhances degradation of viral proteins. When interferon and dexamethasone are both present, no inhibition of the appearance of reverse transcriptase is observed. Thus, dexamethasone has a second effect on virus production, namely to prevent the inhibition by interferon of the appearance of intracellular reverse transcriptase. Since dexamethasone completely overcomes the inhibitory effect of interferon on intracellular reverse transcriptase levels, but only partially reverses the inhibition by interferon of virus production, interferon (in the presence of dexamethasone) must also inhibit a post‐translational step in virus production. This step may or may not be the same as the late dexamethasone‐sensitive step. Thus, both dexamethasone and interferon appear to have both translational (or pre‐translational) and post‐translational effects on the production of xenotropic (v‐2) mouse type‐C virus. This suggests that BALB/c mouse cells restrict the production of xenotropic endogenous virus at two distinct sites.