       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).

