Regulation of foamy viral transcription and RNA export

Foamy viruses (FVs) are distinct members of the retrovirus (RV) family. In this chapter, the molecular regulation of foamy viral transcription, splicing, polyadenylation, and RNA export will be compared in detail to the orthoretroviruses. Foamy viral transcription is regulated in early and late phases, which are separated by the usage of two promoters. The viral transactivator protein Tas activates both promoters. The nature of this early-late switch and the molecular mechanism used by Tas are unique among RVs. RVs duplicate the long terminal repeats (LTRs) during reverse transcription. These LTRs carry both a promoter region and functional poly(A) sites. In order to express full-length transcripts, RVs have to silence the poly(A) signal in the 5' LTR and to activate it in the 3' LTR. FVs have a unique R-region within these LTRs with a major splice donor (MSD) at +51 followed by a poly(A) signal. FVs use a MSD-dependent mechanism to inactivate the polyadenylation. Most RVs express all their genes from a single primary transcript. In order to allow expression of more than one gene from this RNA, differential splicing is extensively used in complex RVs. The splicing pattern of FV is highly complex. In contrast to orthoretroviruses, FVs synthesize the Pol precursor protein from a specific and spliced transcript. The LTR and IP-derived primary transcripts are spliced into more than 15 different mRNA species. Since the RNA ratios have to be balanced, a tight regulation of splicing is required. Cellular quality control mechanisms retain and degrade unspliced or partially spliced RNAs in the nucleus. In this review, I compare the RNA export pathways used by orthoretroviruses with the distinct RNA export pathway used by FV. All these steps are highly regulated by host and viral factors and set FVs apart from all other RVs.