Control of the ppp(a2'p)nA system in HeLa cells. Effects of interferon and virus infection.

Abstract

HeLa cells have an unusually high level of ppp(A2'p)nA synthetase (n = 2 to greater than or equal to 4) even in the absence of interferon treatment. In accord with this ppp(A2'p)nA and ppp(A2'p)nA-mediated ribosomal RNA cleavage occur naturally in response to encephalomyocarditis virus infection in control as well as in interferon-treated cells. Despite this, in the absence of interferon treatment, encephalomyocarditis virus grows well in these cells. A possible explanation for this paradox is that the ppp(A2'p)nA dependent RNase is lost or inactivated at later times post-infection in control but not in interferon-treated cells. It appears, therefore, to be the prevention by interferon of the virus-mediated inhibition of the ppp(A2'p)n-dependent nuclease rather than the absolute level or induction of the ppp(A2'p)nA synthetase which is crucial for the activity of the ppp(A2'p)nA system in HeLa cells. These results provide evidence for a further level of control in the ppp(A2'p)nA system and show that limited ppp(A2'p)nA-mediated ribosomal RNA cleavage alone is not sufficient to cause an inhibition of virus growth.