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Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy

Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive t...

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Autores principales: Johnson, Edward M., Wortman, Margaret J., Dagdanova, Ayuna V., Lundberg, Patric S., Daniel, Dianne C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649189/
https://www.ncbi.nlm.nih.gov/pubmed/23690820
http://dx.doi.org/10.1155/2013/197807
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author Johnson, Edward M.
Wortman, Margaret J.
Dagdanova, Ayuna V.
Lundberg, Patric S.
Daniel, Dianne C.
author_facet Johnson, Edward M.
Wortman, Margaret J.
Dagdanova, Ayuna V.
Lundberg, Patric S.
Daniel, Dianne C.
author_sort Johnson, Edward M.
collection PubMed
description Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR) of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence.
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spelling pubmed-36491892013-05-20 Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy Johnson, Edward M. Wortman, Margaret J. Dagdanova, Ayuna V. Lundberg, Patric S. Daniel, Dianne C. Clin Dev Immunol Review Article Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR) of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence. Hindawi Publishing Corporation 2013 2013-04-15 /pmc/articles/PMC3649189/ /pubmed/23690820 http://dx.doi.org/10.1155/2013/197807 Text en Copyright © 2013 Edward M. Johnson et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Johnson, Edward M.
Wortman, Margaret J.
Dagdanova, Ayuna V.
Lundberg, Patric S.
Daniel, Dianne C.
Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title_full Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title_fullStr Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title_full_unstemmed Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title_short Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy
title_sort polyomavirus jc in the context of immunosuppression: a series of adaptive, dna replication-driven recombination events in the development of progressive multifocal leukoencephalopathy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649189/
https://www.ncbi.nlm.nih.gov/pubmed/23690820
http://dx.doi.org/10.1155/2013/197807
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