Decrease of oligo-2',5'-adenylate synthetase activity in BALB3T3 cell persistently infected with Moloney murine...

The induction of oligo-2',5'-adenylate synthetase (2-5AS) activity by interferon (IFN) was decreased in BALB3T3 cells persistently infected with Moloney murine leukemia virus (Mo-MLV) as compared with uninfected cells. Furthermore, the correlation between increased susceptibility to vesicular stomatitis virus (VSV) infection and reduced 2-5AS activity was recognized in the Mo-MLV persistently infected cells. The decrease of enzyme activity was confirmed by a solid phase reaction and an analysis of reaction products by Fast Polynucleotide Liquid Chromatography (FPLC) in addition to a liquid phase reaction. In a solid-phase reaction, the enzyme protein binds to polyinosinate-cytidylate (Poly I:C) agarose beads and other cellular proteins can be washed out from the reaction mixtures. Therefore, these results indicate that the decrease of IFN-induced enzyme activity is due to the suppression of transcription and/or translation of 2-5AS mRNA. A decreased amount of 2-5AS mRNA in persistently infected cells was observed by Northern blot and dot-blot hybridization. On the other hand, cell lysate of Mo-MLV infected cells inhibited the 2-5AS activity in liquid phase reaction. The inhibition may also be partly due to the degradation of oligo-2',5'-adenylate (2-5A) formed by 2-5AS.