title: JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant.
abstract: 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.
authors.affiliation: Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Dang
authors.forename: Christian
authors.initials: C
authors.lastname: Wüthrich
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D005809:Genes, Regulator; D005814:Genes, Viral; D016679:Genome, Viral; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D017966:Pyramidal Cells / Q000821:virology; D017384:Sequence Deletion; D020080:Tandem Repeat Sequences; D014758:Viral Core Proteins / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism; D056189:Viral Tropism; D000086082:Viroporin Proteins
chemical_list: D004279:DNA, Viral; D014758:Viral Core Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins