Impaired Regulation of HLA-DR Expression in Human Immunodeficiency Virus-Infected Monocytes
Abstract
<h2>HIV-1 AFFECTS HLA-DR TRANSCRIPTION</h2> Earlier experiments demonstrated a loss of HLA-DR expression in our model system which was associated with absent HLA-DR mRNA ( 88 ). These observations could be attributed to either a lack of transcription or, alternatively, to mRNA instability. The loss of HLA-DR expression in the human monocytic hybridomas after HIV-1 infection could be overcome by transfection of HLA-DR genes driven by a nonphysiologic cytomegalovirus promoter, suggesting that HIV-1 was having an effect on transcriptional regulation through DNA binding proteins ( 52 ). Much of our knowledge of the regulation of MHC-II gene transcription comes from the study of a rare immunodeficiency known as bare lymphocyte syndrome (BLS) ( 57 ). BLS is characterized by a loss of expression of all MHC-II antigens, resulting in general susceptibility to infection and increased mortality ( 19 ). Genetic analysis of patients with this disease has revealed heterogeneous mutations that segregate outside of the MHC locus ( 8 ). The subsequent identification and characterization of the mutated factors responsible for BLS later explained these findings. Two groups of BLS patients were defined based on their molecular defects (Fig. 1 ). The first group of patients had mutations in