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Journal of Virology, August 2001, p. 6817-6824, Vol. 75, No. 15
Jefferiss Research Trust Laboratories,
Wright-Fleming Institute, Imperial College School of Medicine at St.
Mary's, London W2 1PG, United Kingdom,1 and
Howard Hughes Medical Institute2
and Department of Genetics,3 Duke
University Medical Center, Durham, North Carolina 27710
Received 19 January 2001/Accepted 28 April 2001
It has been suggested that sequences located within the 5'
noncoding region of human foamy virus (HFV) are critical for expression of the viral Gag and Pol structural proteins. Here, we identify a
discrete ~151-nucleotide sequence, located within the R
region of the HFV long terminal repeat, that activates HFV Gag and Pol expression when present in the 5' noncoding region but that is inactive
when inverted or when placed in the 3' noncoding region. Sequences that
are critical for the expression of both Gag and Pol include not
only the 5' splice site positioned at +51 in the R region,
which is used to generate the spliced pol mRNA,
but also intronic R sequences located well 3' to this
splice site. Analysis of total cellular gag and
pol mRNA expression demonstrates that deletion of
the R region has little effect on gag mRNA levels but that R deletions that would be predicted to leave the
pol 5' splice site intact nevertheless inhibit the
production of the spliced pol mRNA. Gag expression
can be largely rescued by the introduction of an intron into the 5'
noncoding sequence in place of the R region but not by an intron or any
one of several distinct retroviral nuclear RNA export sequences
inserted into the mRNA 3' noncoding sequence. Neither the R element
nor the introduced 5' intron markedly affects the cytoplasmic level of
HFV gag mRNA. The poor translational utilization of
these cytoplasmic mRNAs when the R region is not present in
cis also extended to a cat indicator gene
linked to an internal ribosome entry site introduced into the 3'
noncoding region. Together these data imply that the HFV R region acts
in the nucleus to modify the cytoplasmic fate of target
HFV mRNA. The close similarity between the role of the HFV R region
revealed in this study and previous data (M. Butsch, S. Hull, Y. Wang,
T. M. Roberts, and K. Boris-Lawrie, J. Virol. 73:4847-4855, 1999) demonstrating a critical role for the
R region in activating gene expression in the unrelated retrovirus
spleen necrosis virus suggests that several distinct retrovirus
families may utilize a common yet novel mechanism for the
posttranscriptional activation of viral structural protein expression.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.15.6817-6824.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
The R Region Found in the Human Foamy Virus Long Terminal Repeat
Is Critical for both Gag and Pol Protein Expression

*
Corresponding author. Mailing address: Jefferiss
Research Trust Laboratories, Wright-Fleming Institute, Imperial College
School of Medicine at St. Mary's, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 (0) 207 594 3902. Fax: 44 (0) 207 594 3906. E-mail: m.mcclure{at}ic.ac.uk.
Present address: Georg-Speyer-Haus Institute for Biomedical
Research, D-60596 Frankfurt am Main, Germany.
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