We have demonstrated in the murine system, that type C RNA viral sequences are located adjacent to histocompatibility genes. The availability of reagents and the obvious interest on the human histocompatibility system, the HLA gene complex, makes it attractive to address the issue of whether viral sequences also flank H genes in other species by considering the human system. Preliminary studies are presented which demonstrate that viral sequences flank at least some HLA Class I genes. Therefore this grant proposes to: (1) determine the nature and extent of these viral sequences,i.e., do HLA flanking viruses have the complete LTR-gag-pol-env-LTR configuration of most retroviruses; (2) establish whether in such viruses all or some of the reading frames are open; i.e. is it reasonable to expect these viruses to be infectious, or at least that some of their component genes will be expressed as viral antigens; (3) attempt to derive virus-specific probes so that we can study their expression in normal and transformed human cells it has been demonstrated by DNA-RNA hybridization experiments that human cells contain species of poly (A)+ RNA that anneal to retroviral probes). (4) determine whether HLA Class I gene associated viral sequences belong to a broad family of human endogenous retroviruses or are limited to those already detected. (5) if the HLA linked viral sequences belong to a family of endogenous retroviruses, determine the chromosomal location of other members of the family. In the murine system such viruses tend to be mostly associated with histocompatibility (H) and lymphocyte differentiation (Ly) genes This association would be of biological interest per se and might provide an additional approach to clone human H and Ly genes. (6) Finally, we shall attempt to establish whether these viral sequences affect the transcription and expression of HLA Class I genes which they flank and whether these """"""""transposon like"""""""" viral elements play a role in the duplication and gene conversion events associated with Class I genes.
