Differential expression of human endogenous retroviral sequences similar to mouse mammary tumor virus in normal peripheral blood mononuclear cells

Abstract

Mouse mammary tumor virus (MMTV) is a retrovirus that causes breast cancer in certain strains of mice. In a previous study we identified, by sequencing clones from human lymphocytes, six groups with similarities to MMTV. Using a primer pair derived from pol sequences conserved within types A, B, and D retroviruses and probes from the six human MMTV-like (HML-1 to HML-6) groups in an internally controlled hybridization assay we investigated the normal variation of expression in PBMCs. Variations occurred within all groups but was most significant within group HML-1, where hybridization signals differed by more than 500-fold between individuals. Groups HML-2 and HML-3 showed consistently stronger hybridization signals than groups HML-1 and HML-5, while group HML-6 resulted in weak signals for all individuals. Stringent hybridization of the amplified cDNA to 20 individual HML clones also demonstrated a marked heterogeneity of expression. Hybridization signals from some groups and sequences were found to be correlated, either in a positive or negative fashion. RNA isolated from PBMCs collected from two donors at four different time points (in the morning and in the afternoon on the same day, repeated 1 week later) was also analyzed using the six hml probes. A small variation in hybridization signals was seen in samples collected on the same day, but a larger difference was observed in samples taken 1 week later. The correlations and the differences in the expression of HMLs between individuals implicate a complex transcriptional regulation system of these sequences.