Inhibition of HLA class I antigen and mRNA expression induced by Rous sarcoma virus in transformed human fibroblasts

Cells from various human nonlymphoreticular neoplasms show reduced HLA class I antigen expression. In this report, a system of human fibroblasts transformed by an avian retrovirus has been employed to investigate the mechanism of this phenomenon. Rous sarcoma virus has been used to transform in vitro human dermal fibroblasts, and clonal cell lines have been established from these cultures. In all the clones studied the integration of the provirus induced a reduction of cell-surface HLA-A, -B, -C framework antigen and beta 2-microglobulin expression when compared to levels for the respective parental fibroblasts. The reduction was correlated with a diminished intracellular synthesis of these molecules. Uninfected cells derived from an osteogenic sarcoma exhibited a reduced expression comparable to that of dermal diploid fibroblasts obtained from the same donor and transformed by Rous sarcoma virus. RNA gel blot analysis of total cellular RNA and of poly(A)+ cytoplasmic RNA showed a markedly decreased amount of HLA class I transcripts in the transformed cells. Southern blot study of genomic DNAs digested with several restriction endonucleases showed that the banding patterns of the HLA genes were not altered in the cells harboring the Rous sarcoma provirus. Our data are consistent with the hypothesis that the Rous sarcoma provirus that does not seem to be linked to the major histocompatibility complex class I gene superfamily may negatively control HLA gene expression.