Abstract
Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by the viral enzyme reverse transcriptase (RT). This event is a pivotal step in the life cycle of all retroviruses. In contrast to orthoretroviruses, the domain structure of the mature RT of foamy viruses is different, i.e., it harbors the protease (PR) domain at its N-terminus, thus being a PR-RT. This structural feature has consequences on PR activation, since the enzyme is monomeric in solution and retroviral PRs are only active as dimers. This review focuses on the structural and functional aspects of simian and prototype foamy virus reverse transcription and reverse transcriptase, as well as special features of reverse transcription that deviate from orthoretroviral processes, e.g., PR activation.
Highlights
Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by the viral enzyme reverse transcriptase (RT)
In contrast to orthoretroviruses such as human immunodeficiency virus (HIV), the Pol protein is expressed from a separate mRNA
Since the overall amino acid similarity of Foamy viruses (FVs) RTs to Moloney MLV (MoMLV) or Xenotropic murine leukaemia virus-related virus (XMRV) RT is less than 25%, and the PR domain is an integral part of the mature FV enzyme, subdomain assignments cannot be obtained from sequence comparisons
Summary
Foamy viruses (FVs) are retroviruses that—based on several differences in their molecular properties—are gathered in the subfamily of Spumaretrovirinae, whereas all other retroviruses are members of the subfamily Orthoretrovirinae [1]. FVs are complex retroviruses, i.e., they contain accessory genes Similar to orthoretroviruses, their genomes contain the genes gag, pol, and env (Figure 1). The 50 LTR harbors the viral promoter, which controls transcription of the gag, pol, and env mRNAs. FVs possess an internal promoter (IP) near the 30 end of the env gene, which is responsible for transcription of the accessory proteins Bet and Tas [8,9,10,11] (Figure 1). The Bet protein appears to be important for efficient virus replication [13], and interacts with the cellular proteins of the APOBEC family, which function as antiretroviral restriction factors [14,15,16,17,18] Another interesting feature of FVs is the processing of the Gag protein. The gene products Gag and Pol, which are processed by the viral PR, are shown
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