Differential expression of mRNAs for JC virus large and small tumor antigens in brain tissues from progressive multifocal leukoencephalopathy patients with and without AIDS.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 17 ·1994-08-16 ·Pages 8283-7

Ishaq M, Stoner GL

Abstract

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.

MeSH Terms

Acquired Immunodeficiency Syndrome/complications Adult Antigens, Viral/biosynthesis Base Sequence Brain/metabolism,microbiology Child Cloning, Molecular DNA Primers DNA, Viral/isolation & purification Exons Female Gene Expression HIV-1/isolation & purification,metabolism Humans JC Virus/genetics,isolation & purification,metabolism Leukoencephalopathy, Progressive Multifocal/complications,metabolism,microbiology Male Middle Aged Molecular Sequence Data Polymerase Chain Reaction Proviruses/isolation & purification,metabolism RNA, Messenger/biosynthesis,isolation & purification Transcription, Genetic

Chemicals

Antigens, Viral DNA Primers DNA, Viral RNA, Messenger

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Ishaq M

Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stoner G L

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.91.17.8283

Published

1994-08-16

Pages

8283-7

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC44590

Subset

External Links

PubMed source DOI: 10.1073/pnas.91.17.8283 PMC Full Text View journal details

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Differential expression of mRNAs for JC virus large and small tumor antigens in brain tissues from progressive multifocal leukoencephalopathy patients with and without AIDS.

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