Resistance of vaccinia virus to interferons: modulation of the 2-5A system in interferon-treated, vaccinia virus infected cells.
In this study we have examined if resistance of vaccinia virus to interferon (IFN) correlates with virus-induced alterations of the 2-5A system. We have shown that in various IFN-treated vaccinia virus infected cells of mouse, monkey and human origins, the intracellular levels of 2-5A are low early in infection but exhibit a sharp rise late in infection. In spite of the presence of 2-5A, activation of the 2-5A dependent RNase, as measured by the rRNA cleavage assay, does not occur or is delayed in the course of virus infection. However, when cycloheximide, an inhibitor of protein synthesis is added at the time of virus infection, extensive cleavage or rRNA is observed in IFN-treated, infected cells. If cycloheximide is added at various times after virus infection, rRNA cleavage is gradually prevented and a virus-induced inhibitor of the 2-5A system can be detected between 1-2 hr post infection. A function encoded by a ts 22 mutant of vaccinia virus blocked rRNA cleavage. Restriction of rRNA cleavage during virus infection correlated with dephosphorylation of 2-5A. Our findings suggest that modulation of the 2-5A system by vaccinia virus involves the production of an activator and simultaneous synthesis of an inhibitor(s). Viral ds-RNA is likely to be the activator while a function encoded by ts 22 mutant is involved in inhibition of the 2-5A system. Other viral functions (ATPase and phosphatase) may also be involved in modifications of the 2-5A system by regulating 2-5A levels and altering the integrity of 2-5A. Modifications of the 2-5A system, during vaccinia virus infection might contribute to the resistance of this cytoplasmic DNA virus to IFN.
Páez
E
E
Department of Biochemistry, State University of New York Health Science Center, Brooklyn 11203.
Esteban
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004352:Drug Resistance, Microbial; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D012260:Ribonucleases / Q000235:genetics; D014616:Vaccinia virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D012260:Ribonucleases