The mouse genome contains 30-50 copies of endogenous murine leukemia viral (MuLV)-related sequences. Only a few of these represent inducible viral loci. We previously isolated several endogenous MuLV proviruses from BALB/c and AKR/J mouse DNA. Molecular and biochemical characterization of the endogenous MuLV DNAs indicated that about 50% of the cloned DNAs were related to known MuLV proviruses. DNAs belonging to this class could be distinguished from know infectious MuLV DNAs by the presence of a 190 bp insertion in the U3 LTR region, unique restriction sites, and env sequences which were highly related to recombinant mink cell focus-forming (MCF) MuLVs. Chromosomal mapping studies allowed us to locate one of these endogenous MuLV DNAs containing an MCF-type env gene on chromosome 11 in the vicinity of the alpha-hemoglobin gene. This endogenous provirus was absent in mouse strains from which MCF viruses have not been successfully isolated. Analysis of recombinant viruses constructed in vitro demonstrated that the host-range property of MCF MuLVs is due to determinants located in the 5' env. Furthermore, the mink cell focus-inducing ability unique to MCF viruses also resides in the same region of the env gene. A novel class of endogenous MuLV DNAs was identified, distinguishable from other MuLV proviruses based upon absence of restriction sites characteristic of known MuLV proviral DNAs and lack of reactivity to a generalized MuLV LTR DNA probe. Nucleotide sequence analysis indicated that MuLV DNAs comprising this new class had a retroviral-like genomic structure and were distantly related to known MuLV proviruses in their sequence. We are currently studying sequences located at the viral termini of these MuLV LTR-negative DNAs in an effort to identify regulatory elements which may represent potential new LTRs associated with these proviral DNAs. Studies on the regulation of endogenous African green monkey (AGM) LTR expression suggested that the T antigen of SV40 virus may enhance the expression of the LTRs. COS cells that express T Ag contained greatly elevated levels of AGM LTR mRNA when compared to levels present in the parental CV-1 cells which lack T antigen. Further studies of the transcriptional regulation of endogenous LTRs are in progress.
NIH ExPorter
NIH ExPorter