Expression and biological significance of human endogenous retroviral sequences

The human genome contains a variety of elements resembling mammalian retroviruses. Most of these sequences have been found to be related to primate and murine C-type viruses (BaEV, SSAV/GaLV, MuLV), murine B-type viruses and A-type particles (MMTV, IAP), or human T-cell lymphotropic viruses (HTLV). Altogether, human endogenous retroviruses and retroviral elements are estimated to comprise at least 0.1 to 0.6% of the human genome. Like other transposable elements they may contribute in shaping the eukaryotic genome by intracellular transposition events or by generating hot spots of recombination. Human retroviral sequences have been shown to be transcriptionally active, especially in human placenta and embryonic tissue and in human tumor cell lines. Some elements that are coexpressed with cellular sequences are supposed to play a role in regulation of gene expression. Furthermore, expression of human endogenous retroviral sequences may have a protective function against superinfection by related exogenous retroviruses. On the other hand, endogenous retroviruses and retroviral elements represent a cellular reservoir of possibly pathogenic retroviral genes. They may be involved in chromosomal aberrations by acting as sites for recombination events between different chromosomes. Furthermore, they can act as insertion mutagens and activate or inactivate cellular genes. Retroviral gene products themselves may also be pathogenic as has been shown for the immunosuppressive effects of p15E envelope proteins. Therefore, the role of human endogenous retroviruses and retroviral sequences in biological processes is currently a subject of great interest.