Retroviruses in foreign species and the problem of provirus silencing

Retroviruses are known to integrate in the host cell genome as proviruses, and therefore they are prone to cell-mediated control at the transcriptiona l and posttranscriptional levels. This plays an important role especially a fter retrovirus heterotransmission to foreign species, but also to differen tiated cells. In addition to host cell-mediated blocks in provirus expressi on, also so far undefined host specificities, deciding upon the pathogenic manifestation of retrovirus heterotransmission, are in play. In this respec t, we discuss especially the occurrence of wasting disease and immunodefici ency syndrome, which we established also in avian species using avian leuko sis virus subgroup C (ALV-C) inoculated in mid-embryogenesis in duck or chi cken embryos. The problem of provirus downregulation in foreign species or in differentiated cells has been in the recent years approached experimenta lly. From a series of observations it became apparent that provirus downreg ulation is mediated by its methylation, especially in the region of provira l enhancer-promoter located in long terminal repeats (LTR). Several strateg ies have been devised in order to protect the provirus from methylation usi ng LTR modification and/or introducing in the LTR sequence motifs acting as antimethylation tags. In such a way the expression of retroviruses and vec tors in foreign species, as well as in differentiated cells, has been signi ficantly improved. The complexity of the mechanisms involved in provirus do wnregulation and further possibilities to modulate it are discussed. (C) 20 00 Elsevier Science B.V. All rights reserved.