Retroviral DNA Transposition: Themes and Variations.

Retroviruses and LTR retrotransposons are transposable elements that encapsidate the RNAs that are intermediates in the transposition of DNA copies of their genomes (proviruses), from one cell (or one locus) to another. Mechanistic similarities in DNA transposase enzymes and retroviral/retrotransposon integrases underscore the close evolutionary relationship among these elements. The retroviruses are very ancient infectious agents, presumed to have evolved from Ty3/Gypsy LTR retrotransposons (1), and DNA copies of their sequences can be found embedded in the genomes of most, if not all, members of the tree of life. All retroviruses share a specific gene arrangement and similar replication strategies. However, given their ancestries and occupation of diverse evolutionary niches, it should not be surprising that unique sequences have been acquired in some retroviral genomes and that the details of the mechanism by which their transposition is accomplished can vary. While every step in the retrovirus lifecycle is, in some sense, relevant to transposition, this Chapter focuses mainly on the early phase of retroviral replication, during which viral DNA is synthesized and integrated into its host genome. Some of the initial studies that set the stage for current understanding are highlighted, as well as more recent findings obtained through use of an ever-expanding technological toolbox including genomics, proteomics, and siRNA screening. Persistence in the area of structural biology has provided new insight into conserved mechanisms as well as variations in detail among retroviruses, which can also be instructive.