JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.

JC virus encephalopathy (JCVE) is a newly described gray matter disease of the brain caused by productive infection of cortical pyramidal neurons. We characterized the full length sequence of JCV isolated from the brain of a JCVE patient, analyzed its distribution in various compartments by PCR, and...

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Main Authors: Xin Dang, Christian Wüthrich, Jennifer Gordon, Hirofumi Sawa, Igor J Koralnik
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3334910?pdf=render
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author Xin Dang
Christian Wüthrich
Jennifer Gordon
Hirofumi Sawa
Igor J Koralnik
author_facet Xin Dang
Christian Wüthrich
Jennifer Gordon
Hirofumi Sawa
Igor J Koralnik
author_sort Xin Dang
collection DOAJ
description JC virus encephalopathy (JCVE) is a newly described gray matter disease of the brain caused by productive infection of cortical pyramidal neurons. We characterized the full length sequence of JCV isolated from the brain of a JCVE patient, analyzed its distribution in various compartments by PCR, and determined viral gene expression in the brain by immunohistochemistry(IHC). We identified a novel JCV variant, JCV(CPN1), with a unique 143 bp deletion in the Agno gene encoding a truncated 10 amino acid peptide, and harboring an archetype-like regulatory region. This variant lacked one of three nuclear protein binding regions in the Agno gene. It was predominant in the brain, where it coexisted with an Agno-intact wild-type strain. Double immunostaining with anti-Agno and anti- VP1 antibodies demonstrated that the truncated JCV(CPN1) Agno peptide was present in the majority of cortical cells productively infected with JCV. We then screened 68 DNA samples from 8 brain, 30 CSF and 30 PBMC samples of PML patients, HIV+ and HIV- control subjects. Another JCV(CPN) strain with a different pattern of Agno-deletion was found in the CSF of an HIV+/PML patient, where it also coexisted with wild-type, Agno-intact JCV. These findings suggest that the novel tropism for cortical pyramidal neurons of JCV(CPN1), may be associated with the Agno deletion. Productive and lytic infection of these cells, resulting in fulminant JCV encephalopathy and death may have been facilitated by the co-infection with a wild-type strain of JCV.
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spelling doaj.art-d69159b5201b49cc896f855b2f24d3a32022-12-21T19:34:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3579310.1371/journal.pone.0035793JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.Xin DangChristian WüthrichJennifer GordonHirofumi SawaIgor J KoralnikJC virus encephalopathy (JCVE) is a newly described gray matter disease of the brain caused by productive infection of cortical pyramidal neurons. We characterized the full length sequence of JCV isolated from the brain of a JCVE patient, analyzed its distribution in various compartments by PCR, and determined viral gene expression in the brain by immunohistochemistry(IHC). We identified a novel JCV variant, JCV(CPN1), with a unique 143 bp deletion in the Agno gene encoding a truncated 10 amino acid peptide, and harboring an archetype-like regulatory region. This variant lacked one of three nuclear protein binding regions in the Agno gene. It was predominant in the brain, where it coexisted with an Agno-intact wild-type strain. Double immunostaining with anti-Agno and anti- VP1 antibodies demonstrated that the truncated JCV(CPN1) Agno peptide was present in the majority of cortical cells productively infected with JCV. We then screened 68 DNA samples from 8 brain, 30 CSF and 30 PBMC samples of PML patients, HIV+ and HIV- control subjects. Another JCV(CPN) strain with a different pattern of Agno-deletion was found in the CSF of an HIV+/PML patient, where it also coexisted with wild-type, Agno-intact JCV. These findings suggest that the novel tropism for cortical pyramidal neurons of JCV(CPN1), may be associated with the Agno deletion. Productive and lytic infection of these cells, resulting in fulminant JCV encephalopathy and death may have been facilitated by the co-infection with a wild-type strain of JCV.http://europepmc.org/articles/PMC3334910?pdf=render
spellingShingle Xin Dang
Christian Wüthrich
Jennifer Gordon
Hirofumi Sawa
Igor J Koralnik
JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
PLoS ONE
title JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
title_full JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
title_fullStr JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
title_full_unstemmed JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
title_short JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
title_sort jc virus encephalopathy is associated with a novel agnoprotein deletion jcv variant
url http://europepmc.org/articles/PMC3334910?pdf=render
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AT hirofumisawa jcvirusencephalopathyisassociatedwithanovelagnoproteindeletionjcvvariant
AT igorjkoralnik jcvirusencephalopathyisassociatedwithanovelagnoproteindeletionjcvvariant