Selective disruption of growth hormone transcription machinery by viral infection.
Viruses that establish persistent infections may show selective and unique effects on the host's transcriptional machinery. Lymphocytic choriomeningitis virus (LCMV), a noncytolytic virus, can persistently infect a rat pituitary cell line. Although the infected cells remain free of structural damage, virus markedly interferes with growth hormone (GH) but only minimally interferes with prolactin transcription. The study of GH promoter-chloramphenicol acetyltransferase-transfected cells and GH promoter deletion mutants demonstrates that the viral effect is at the level of GH promoter and is due to interference with GH transactivator factor GHF1 (Pit1). Treatment of LCMV-infected cells with the antiviral agent ribavirin cures the infection and restores normal GH mRNA levels. These results illustrate a molecular mechanism by which a virus infection can disrupt synthesis of a cell's differentiated product without perturbing vital cellular functions.
de la Torre
J C
JC
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Oldstone
M B
MB
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D013006:Growth Hormone / Q000235:genetics*; D066298:In Vitro Techniques; D008216:Lymphocytic Choriomeningitis / Q000235:genetics*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010902:Pituitary Gland / Q000166:cytology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; C494186:Pou1f1 protein, rat; D012333:RNA, Messenger; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D013006:Growth Hormone