Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.
Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and beta 2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene.
D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics*; D007372:Interferons / Q000096:biosynthesis; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics*; D008980:Moloney murine sarcoma virus / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D009053:Sarcoma Viruses, Murine / Q000235:genetics*; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D007372:Interferons; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase