Progressive multifocal leukoencephalopathy in human immunodeficiency virus type 1-infected patients: absence of correlation between JC virus neurovirulence and polymorphisms in the transcriptional control region and the major capsid protein loci.

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rapidly fatal demyelinating disease of the central nervous system related to JC polyomavirus (JCV) replication in oligodendrocytes. PML usually occurs in immunocompromised individuals, especially in the setting of AIDS. Administration of highly active anti-retroviral therapy (HAART) may improve survival prognosis in some, but not all, patients with AIDS-related PML. This observation might be explained by the outgrowth of some JCV variants of increased fitness. To evaluate this hypothesis, two subgroups of five patients with AIDS-related PML, started on HAART after PML diagnosis, were analysed. The non-responder (NR) patients died rapidly despite HAART, while responders (R) had a positive outcome and were still alive. JCV DNA was extracted from cerebrospinal fluid biopsies and two regions of the genome were analysed, the transcriptional control region (TCR) and the major capsid protein gene (VP1). Both regions show different degrees of polymorphism and are recognized as evolving independently. Sequence analysis demonstrated that (i) extensive TCR rearrangements were present in both subgroups of patients, (ii) VP1 sequence polymorphisms could be identified in the BC loop, suggesting the absence of immune selection, and (iii) no genomic marker for JCV specific neurovirulence could be identified in the TCR and VP1 loci.

• Authors: Monica Sala, Jean-Pierre Vartanian, Pascale Kousignian, Jean-François Delfraissy, Yassine Taoufik, Simon Wain-Hobson, Jacques Gasnault
• Journal: The Journal of general virology (J Gen Virol) Vol. 82 Issue Pt 4 Pg. 899-907 (Apr 2001) ISSN: 0022-1317 [Print] England
• PMID: 11257196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Plant Proteins
• Trans-Activators
• Transcription Factors

Topics

• Acquired Immunodeficiency Syndrome (complications)
• Base Sequence
• Chromosome Mapping
• DNA-Binding Proteins (genetics)
• HIV-1
• Humans
• JC Virus (genetics, pathogenicity)
• Leukoencephalopathy, Progressive Multifocal (virology)
• Molecular Sequence Data
• Plant Proteins
• Polymorphism, Genetic
• Trans-Activators
• Transcription Factors (genetics)
• Transcription, Genetic
• Virulence