Document 0363 DOCN M9490363 TI Differential expression of mRNAs for JC virus large and small tumor antigens in brain tissues from progressive multifocal leukoencephalopathy patients with and without AIDS. DT 9411 AU Ishaq M; Stoner GL; Laboratory of Experimental Neuropathology, National Institute of; Neurological Disorders and Stroke, National Institutes of Health,; Bethesda, MD 20892. SO Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8283-7. Unique Identifier : AIDSLINE MED/94336730 AB JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), the fatal demyelinating infection of oligodendrocytes, in up to 5% of AIDS patients. An intron-differential RNA PCR was developed to study the expression of alternately spliced JCV early mRNAs in brain tissues from PML patients with and without AIDS and in JCV-induced hamster brain tumors. The method utilizes primers that span the large tumor (T) and small tumor (t) antigen introns allowing amplification of specific cDNAs in the presence of contaminating viral genomic DNA. Hybridization with specific junctional probes and DNA sequence analysis confirmed the identity of the PCR products. Sequencing showed that JCV early mRNA is alternatively spliced as previously predicted by analogy to simian virus 40. Large T antigen mRNA was detected in all the brain tissues from PML patients with and without AIDS. The expression of small t antigen mRNA varied depending upon the association of PML with AIDS and upon other unknown factors. Of the 12 PML/AIDS brain tissue samples, 11 (92%) expressed small t antigen mRNA, whereas only 8 of 13 (62%) brain samples from patients with PML alone showed detectable levels of small t antigen mRNA. Human immunodeficiency virus 1 proviral DNA was detected in 10 of 12 PML/AIDS brain samples. The results indicate that alternative splicing of JCV early mRNA is regulated in the human brain and that the production of small t antigen may not be essential for the pathogenesis of PML. DE Acquired Immunodeficiency Syndrome/*COMPLICATIONS Adult Antigens, Viral/*BIOSYNTHESIS Base Sequence Brain/METABOLISM/*MICROBIOLOGY Child Cloning, Molecular Comparative Study DNA Primers DNA, Viral/*ISOLATION & PURIF Exons Female *Gene Expression Human HIV-1/*ISOLATION & PURIF/METABOLISM Leukoencephalopathy, Progressive Multifocal/COMPLICATIONS/ METABOLISM/*MICROBIOLOGY Male Middle Age Molecular Sequence Data Polymerase Chain Reaction Polyomavirus hominis 2/GENETICS/ISOLATION & PURIF/*METABOLISM Proviruses/ISOLATION & PURIF/METABOLISM RNA, Messenger/*BIOSYNTHESIS/ISOLATION & PURIF Transcription, Genetic JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).