RNA methylation in vaccinia virus-infected chick embryo fibroblasts treated with homologous interferon

Abstract

Interferon-pretreatment of vaccinia-infected chick embryo fibroblasts resulted in a greater than 50% decrease in ribose methylation of the penultimate "cap" nucleotide in virus-specific mRNA. However, in contrast to results obtained with cell-free systems, in intact infected cells there was (a) no detectable reduction in methylation of the 5'-ultimate m7G of viral mRNA; (b) a virus specificity of the interferon-induced change in mRNA "CAP"-methylation seems unlikely and (c) analysis of the ribosomal and transfer RNA fractions isolated from interferon-treated and control cells revealed identical patterns of methylated nucleotides. Thus, the interferon-induced change in methylation is specific for mRNA "CAPS".

Enhanced therapeutic efficacy of poly(ICLC) and ribavirin combinations against Rift Valley fever virus infection in mice

“…Postinfection therapy with low doses of ribavirin or poly(ICLC) alone failed to protect mice effectively. However, enhanced therapeutic activity can be achieved by the use of the two drugs in combination, presumably by inhibiting viral proliferation by simultaneous blocking of different capping events (2,8,14,15). Enhancement of the therapeutic efficacy by combination therapy with compounds having different modes of action offers an attractive therapeutic approach for treatment of human disease.…”

“…Interferon blocks mRNA capping by inhibiting transmethylation reactions (2,8,14), although this may be just one enzyme-related mechanism by which interferon can control viral proliferation (6). Ribavirin is also known to inhibit capping of mRNA by the inhibition of guanylyl transferase (14,15).…”

Biochemistry of Interferons and Their Actions

“…In the case of reovirus and vaccinia virus, the 2-0-methylation of ribose moieties is decreased (62,63); in that ofVS virus the 7-methylation of the 5' terminal guanylate residues is decreased. The nonmethylated VS virus mRNA cannot be translated efficiently, since it is located mainly in the nonpolysomal fraction (64).…”

“…Other effects of IFNs on cells include an alteration in the methylation of viral (and perhaps host) mRNAs (60)(61)(62)(63)(64)(65) and a decrease in the proportion of unsaturated fatty acids in membrane phospholipids, which results in a change in the rigidity of the cell membrane (66,67). The agents mediating these alterations and the role of the alterations in IFN action remain to be elucidated.…”

The interferon renaissance: molecular aspects of induction and action.

“…Variants of this structure are additionally methylated at the preceding two positions and are referred to as cap 0 (m7GpppXpYpZp), cap I (m7GpppXmpYpZp), and cap II (m7GpppXmpYmpZp), where X, Y, and Z represent the three 5'-terminal bases. Kroath et al (131,132) have shown an impairnent of the conversion of cap 0 to cap I in vaccinia virusinfected chicken embryo fibroblasts, and Desrosiers and Lengyel (62) have shown an inhibition of the conversion to cap II in reovirusinfected mouse fibroblasts. The reason for the apparent discrepancy is not clear.…”