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.
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.
Sala
Monica
M
Unité de Rétrovirologie Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Vartanian
Jean-Pierre
JP
Unité de Rétrovirologie Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Kousignian
Pascale
P
Service de Médecine Interne, Hôpital Universitaire de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France3.
Delfraissy
Jean-François
JF
Service de Médecine Interne, Hôpital Universitaire de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France3.|Laboratoire Virus Neurone et Immunité, Faculté de Médecine Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France2.
Taoufik
Yassine
Y
Laboratoire Virus Neurone et Immunité, Faculté de Médecine Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France2.
Wain-Hobson
Simon
S
Unité de Rétrovirologie Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Gasnault
Jacques
J
Service de Médecine Interne, Hôpital Universitaire de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France3.|Laboratoire Virus Neurone et Immunité, Faculté de Médecine Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France2.
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D001483:Base Sequence; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000472:pathogenicity*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008969:Molecular Sequence Data; D010940:Plant Proteins; D011110:Polymorphism, Genetic; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014774:Virulence
D004268:DNA-Binding Proteins; D010940:Plant Proteins; D015534:Trans-Activators; D014157:Transcription Factors