Determination of JC virus non coding control region variants in cerebrolspinal fluid and urine of adult progressive multifocal leukoencephalopathy patients at the university teaching hosipital

Abstract

John Cunningham virus (JC virus) is a polyomavirus that causes Progressive Multifocal Leukoencephalopathy (PML) a debilitating and often fatal disease of the central nervous system. JC virus is ubiquitous, approximately 50% of adults globally have antibodies against the virus and about 30% actively shed the virus in urine. PML develops in patients with immunological impairment such as those infected with Human Immunodeficiency Virus (HIV), patients with hematological malignancies and recipients of immunosuppressive drugs. JC virus has two variants archetype and rearranged which significantly play a critical role in the development of PML. This study was carried out to determine the JC virus variants present in cerebrospinal fluid (CSF) and urine of adult PML patients at the University Teaching Hospital. This was a cross-sectional study of adult patients at the University Teaching Hospital (UTH) who presented with symptoms of central nervous system infections requiring a lumbar puncture and met the inclusion criteria. A total of 326 patients who submitted urine and blood samples besides the CSF were enrolled. Polymerase chain reaction (PCR) to detect JC virus was done on all the CSF samples using the Corbett rotorgene thermal cycler. A second PCR on urine and CSF samples was done on all JC virus positive CSF using primers that detect JC virus archetype variant. Two hundred and seventy five (275) of the 326 were human immunodeficiency virus HIV antibody positive. Five (5) of the sampled CSF had detectable JC virus DNA. All the 5 JC virus from CSF had rearranged NCCR. Four out of the 5 (80%) had detectable JC virus DNA in urine 3 of which were archetype and 1 was rearranged NCCR. The median CD4 was 108.2 cells/ mm³. These findings suggest a much lower prevalence of JC virus compared to Europe and North America where seropositivity is about 50%. The study underlies and further implicates genetic rearrangements of the JC virus being responsible for the neuropathogenesis of JC virus in immunocompromised individuals especially those with HIV or AIDS disease.