
<ArticleTitle>The R region found in the human foamy virus long terminal repeat is critical for both <prot>Gag</prot> and <prot>Pol</prot> protein expression.</ArticleTitle>
<AbstractText>It has been suggested that sequences located within the 5' noncoding region of human foamy virus (HFV) are critical for expression of the viral <prot>Gag</prot> and <prot>Pol</prot> structural proteins. Here, we identify a discrete approximately 151-nucleotide sequence, located within the R region of the HFV long terminal repeat, that activates HFV <prot>Gag</prot> and <prot>Pol</prot> 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 <prot>Gag</prot> and <prot>Pol</prot> include not only the 5' splice site positioned at +51 in the R region, which is used to generate the spliced <prot>pol</prot> mRNA, but also intronic R sequences located well 3' to this splice site. Analysis of total cellular <prot>gag</prot> and <prot>pol</prot> mRNA expression demonstrates that deletion of the R region has little effect on <prot>gag</prot> mRNA levels but that R deletions that would be predicted to leave the <prot>pol</prot> 5' splice site intact nevertheless inhibit the production of the spliced <prot>pol</prot> mRNA. <prot>Gag</prot> 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 <prot>gag</prot> 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.</AbstractText>
