Inhibition of RNA and interferon synthesis in Krebs-2 cells infected with vesicular stomatitis virus

Interferon was detected in suspended cultures of Krebs-2 carcinoma cells by 3–4 hours after infection with an avirulent strain of Newcastle disease virus (NDV). Thereafter, the increase in concentration of interferon was approximately linear and reached a peak within 20 hours. Interferon synthesis was completely inhibited by actinomycin added to the medium within 4 hours after induction but not at 6 or 8 hours. When NDV-induced cells were superinfected with virulent vesicular stomatitis (VS) virus at a multiplicity of 50, interferon synthesis was shut off at exactly the same times as it was by actinomycin. The failure of actinomycin or VS virus to suppress continuing interferon synthesis later than 4 hours after NDV induction suggests that an interferon-specific messenger RNA is transcribed early in this system and continues to function in the presence of the inhibitors.Krebs-2 cells infected with VS virus exhibited a rapid decline in rate of cellular RNA synthesis similar to, but less pronounced than, that caused by actinomycin. Interferon-inducing doses of NDV did not appreciably alter cellular RNA synthesis for at least 3 hours. Inactivation of the infectivity of VS virus by ultraviolet light did not impair its capacity to inhibit cellular RNA and interferon synthesis.These studies suggest that avirulent NDV switches on the interferon-synthesizing capacity of Krebs-2 cells, whereas virulent VS virus switches it off (prevents the switching on) by inhibiting cellular RNA synthesis.