Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.

Détails

ID Serval
serval:BIB_C7A6237D7315
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.
Périodique
Neurology
Auteur(s)
Du Pasquier R.A., Corey S., Margolin D.H., Williams K., Pfister L.A., De Girolami U., Mac Key J.J., Wüthrich C., Joseph J.T., Koralnik I.J.
ISSN
1526-632X[electronic], 0028-3878[linking]
Statut éditorial
Publié
Date de publication
09/2003
Peer-reviewed
Oui
Volume
61
Numéro
6
Pages
775-782
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.
Mots-clé
Acquired Immunodeficiency Syndrome/complications, Acquired Immunodeficiency Syndrome/drug therapy, Adult, Anti-HIV Agents/therapeutic use, Antiviral Agents/therapeutic use, Astrocytes/virology, Capsid/ultrastructure, Cerebellum/virology, DNA, Viral/analysis, Disease Progression, Fatal Outcome, HIV-1, Humans, In Situ Hybridization, Inclusion Bodies, Viral, JC Virus/isolation &amp, purification, JC Virus/physiology, Leukoencephalopathy, Progressive Multifocal/complications, Leukoencephalopathy, Progressive Multifocal/drug therapy, Male, Microscopy, Electron, Neurons/virology, Oligodendroglia/virology, Organ Specificity, Virus Activation, Virus Replication
Pubmed
Web of science
Création de la notice
25/01/2008 15:56
Dernière modification de la notice
03/03/2018 21:19
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