Nucleic Acids Research, Vol 27, Issue 22 4369-4375, Copyright © 1999 by Oxford University Press
F Terenzi, MJ deVeer, H Ying, NP Restifo, BR Williams and RH Silverman
Expression of transfected genes is shown to be suppressed by two
intracellular enzymes, RNase L and protein kinase PKR, which function in
interferon-treated cells to restrict viral replication. RNase L(-/-) or
PKR(-/-) murine embryonic fibroblasts produced enhanced levels of protein
from transfected genes compared with wild-type cells. Increased expression
of exogenous genes in RNase L(-/-) cells correlated with elevated levels of
mRNA and thus appeared to be due to enhanced mRNA stability. Plasmid
encoding adenovirus VA RNAs was able to further enhance accumulation of the
exogenous gene transcript and protein, even in cells lacking PKR. In
contrast to the increased expression of transfected genes in cells lacking
RNase L or PKR, expression of endogenous host genes was unaffected by the
absence of these enzymes. In addition, a dominant-negative PKR mutant
improved expression from a conventional plasmid vector and from a Semliki
Forest virus derived, self-replicating vector. These results indicate that
viral infections and transfections produce similar stress responses in
mammalian cells and suggest strategies for selectively increasing
expression of exogenous genes.
ARTICLES
The antiviral enzymes PKR and RNase L suppress gene expression from viral and non-viral based vectors
Department of Cancer Biology, NB40, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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