Cargando…
Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity
Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease caused by lytic infection of oligodendrocytes with JC virus (JCV). The development of PML in non-immunosuppressed individuals is a growing concern with reports of mortality in patients treated with mAb therapies...
Autores principales: | , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Society for General Microbiology
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052566/ https://www.ncbi.nlm.nih.gov/pubmed/20826618 http://dx.doi.org/10.1099/vir.0.023184-0 |
_version_ | 1782199690488446976 |
---|---|
author | Marshall, Leslie J. Dunham, Lisa Major, Eugene O. |
author_facet | Marshall, Leslie J. Dunham, Lisa Major, Eugene O. |
author_sort | Marshall, Leslie J. |
collection | PubMed |
description | Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease caused by lytic infection of oligodendrocytes with JC virus (JCV). The development of PML in non-immunosuppressed individuals is a growing concern with reports of mortality in patients treated with mAb therapies. JCV can persist in the kidneys, lymphoid tissue and bone marrow. JCV gene expression is restricted by non-coding viral regulatory region sequence variation and cellular transcription factors. Because JCV latency has been associated with cells undergoing haematopoietic development, transcription factors previously reported as lymphoid specific may regulate JCV gene expression. This study demonstrates that one such transcription factor, Spi-B, binds to sequences present in the JCV promoter/enhancer and may affect early virus gene expression in cells obtained from human brain tissue. We identified four potential Spi-B-binding sites present in the promoter/enhancer elements of JCV sequences from PML variants and the non-pathogenic archetype. Spi-B sites present in the promoter/enhancers of PML variants alone bound protein expressed in JCV susceptible brain and lymphoid-derived cell lines by electromobility shift assays. Expression of exogenous Spi-B in semi- and non-permissive cells increased early viral gene expression. Strikingly, mutation of the Spi-B core in a binding site unique to the Mad-4 variant was sufficient to abrogate viral activity in progenitor-derived astrocytes. These results suggest that Spi-B could regulate JCV gene expression in susceptible cells, and may play an important role in JCV activity in the immune and nervous systems. |
format | Text |
id | pubmed-3052566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Society for General Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30525662011-12-01 Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity Marshall, Leslie J. Dunham, Lisa Major, Eugene O. J Gen Virol Animal Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease caused by lytic infection of oligodendrocytes with JC virus (JCV). The development of PML in non-immunosuppressed individuals is a growing concern with reports of mortality in patients treated with mAb therapies. JCV can persist in the kidneys, lymphoid tissue and bone marrow. JCV gene expression is restricted by non-coding viral regulatory region sequence variation and cellular transcription factors. Because JCV latency has been associated with cells undergoing haematopoietic development, transcription factors previously reported as lymphoid specific may regulate JCV gene expression. This study demonstrates that one such transcription factor, Spi-B, binds to sequences present in the JCV promoter/enhancer and may affect early virus gene expression in cells obtained from human brain tissue. We identified four potential Spi-B-binding sites present in the promoter/enhancer elements of JCV sequences from PML variants and the non-pathogenic archetype. Spi-B sites present in the promoter/enhancers of PML variants alone bound protein expressed in JCV susceptible brain and lymphoid-derived cell lines by electromobility shift assays. Expression of exogenous Spi-B in semi- and non-permissive cells increased early viral gene expression. Strikingly, mutation of the Spi-B core in a binding site unique to the Mad-4 variant was sufficient to abrogate viral activity in progenitor-derived astrocytes. These results suggest that Spi-B could regulate JCV gene expression in susceptible cells, and may play an important role in JCV activity in the immune and nervous systems. Society for General Microbiology 2010-12 /pmc/articles/PMC3052566/ /pubmed/20826618 http://dx.doi.org/10.1099/vir.0.023184-0 Text en Copyright © 2010, SGM |
spellingShingle | Animal Marshall, Leslie J. Dunham, Lisa Major, Eugene O. Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title | Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title_full | Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title_fullStr | Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title_full_unstemmed | Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title_short | Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity |
title_sort | transcription factor spi-b binds unique sequences present in the tandem repeat promoter/enhancer of jc virus and supports viral activity |
topic | Animal |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052566/ https://www.ncbi.nlm.nih.gov/pubmed/20826618 http://dx.doi.org/10.1099/vir.0.023184-0 |
work_keys_str_mv | AT marshalllesliej transcriptionfactorspibbindsuniquesequencespresentinthetandemrepeatpromoterenhancerofjcvirusandsupportsviralactivity AT dunhamlisa transcriptionfactorspibbindsuniquesequencespresentinthetandemrepeatpromoterenhancerofjcvirusandsupportsviralactivity AT majoreugeneo transcriptionfactorspibbindsuniquesequencespresentinthetandemrepeatpromoterenhancerofjcvirusandsupportsviralactivity |