J Virol, February 1998, p. 1036-1042, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Center for Agricultural Molecular Biology1 and Department of Plant Pathology,2 Cook College, Rutgers University, New Brunswick, New Jersey 08903-0231, and Department of Molecular Genetics and Microbiology3 and Graduate Program in Molecular Biosciences at Rutgers/University of Medicine and Dentistry of New Jersey,4 University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854
Received 21 August 1997/Accepted 25 October 1997
Programmed ribosomal frameshifting is a molecular mechanism that is
used by many RNA viruses to produce Gag-Pol fusion proteins. The
efficiency of these frameshift events determines the ratio of viral Gag
to Gag-Pol proteins available for viral particle morphogenesis, and
changes in ribosomal frameshift efficiencies can severely inhibit virus
propagation. Since ribosomal frameshifting occurs during the elongation
phase of protein translation, it is reasonable to hypothesize that
agents that affect the different steps in this process may also have an
impact on programmed ribosomal frameshifting. We examined the molecular
mechanisms governing programmed ribosomal frameshifting by using two
viruses of the yeast Saccharomyces cerevisiae. Here, we
present evidence that pokeweed antiviral protein (PAP), a single-chain
ribosomal inhibitory protein that depurinates an adenine residue in the
-sarcin loop of 25S rRNA and inhibits translocation, specifically
inhibits Ty1-directed +1 ribosomal frameshifting in intact
yeast cells and in an in vitro assay system. Using an in vivo assay for
Ty1 retrotransposition, we show that PAP specifically
inhibits Ty1 retrotransposition, suggesting that
Ty1 viral particle morphogenesis is inhibited in infected
cells. PAP does not affect programmed
1 ribosomal frameshift
efficiencies, nor does it have a noticeable impact on the ability of
cells to maintain the M1-dependent killer virus phenotype,
suggesting that
1 ribosomal frameshifting does not occur after the
peptidyltransferase reaction. These results provide the first evidence
that PAP has viral RNA-specific effects in vivo which may be
responsible for the mechanism of its antiviral activity.
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