The Viral Analysis Unit of the LMMN has evaluated over 3500 clinical samples including CSF, plasma and serum for the detection of JC Virus genome sequences. This finding is diagnostic for PML, a rare but mostly fatal disease of the brain, as well as indicating the viral course of infection in many tissue compartments. The LMMN receives many such samples from around the world in circumstances in which diagnosis and pathogenesis cannot be made on clear clinical findings alone. The VAU has made hundreds of determinations on such samples and made the diagnosis on complex cases that provided critical information to neurologists and their patients for future medical care and treatment. In a survey of hundreds of plasma samples, it became clear that over 2% of the population worldwide can be viremic and that approximately 1% of the population is persistently viremic. Such numbers in a well defined and reliable assay system. The nature of the treatment that such viremic patients may receive for underlying diseases particularly that are classified as autoimmune diseases i.e. Multiple Sclerosis, Rheumatoid arthritis, Crohn's disease, Systemic Lupus Erythymatosis. Of the 165 MS patients that developed PML while treated with natalizumab,over half were diagnosed with the data from the Viral Analysis Unit. There have been at least 16 of these patients that had been misdiagnosed and not given correct medical treatment until the VAU provided the correct evidence of PML. Also the cumulative longitudinal data from this work has established that many PML patients never clear their infection even if immune reconstitution is establihsed. In some cases, patients show clinical signs of disease years after the initial diagnosis. This occurs in both HIV/AIDS cases as well as MS cases of PML and warrants close neurological evaluation at annual or sooner time points.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2011
Total Cost
$1,932,812
Indirect Cost
City
State
Country
Zip Code
Soleimani-Meigooni, David N; Schwetye, Katherine E; Angeles, Maria Reyes et al. (2017) JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7. J Neurovirol 23:141-146
Darbinyan, Armine; Major, Eugene O; Morgello, Susan et al. (2016) BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency. Acta Neuropathol Commun 4:73
Major, Eugene O; Nath, Avindra (2016) A link between long-term natalizumab dosing in MS and PML: Putting the puzzle together. Neurol Neuroimmunol Neuroinflamm 3:e235
Zerbe, Christa S; Marciano, Beatriz E; Katial, Rohit K et al. (2016) Progressive Multifocal Leukoencephalopathy in Primary Immune Deficiencies: Stat1 Gain of Function and Review of the Literature. Clin Infect Dis 62:986-94
Turnquist, C; Horikawa, I; Foran, E et al. (2016) p53 isoforms regulate astrocyte-mediated neuroprotection and neurodegeneration. Cell Death Differ 23:1515-28
Patera, Andriani C; Butler, Scott L; Cinque, Paola et al. (2015) 2nd International Conference on Progressive Multifocal Leukoencephalopathy (PML) 2015: JCV virology, progressive multifocal leukoencephalopathy pathogenesis, diagnosis and risk stratification, and new approaches to prevention and treatment. J Neurovirol 21:702-5
Ryschkewitsch, Caroline F; Jensen, Peter N; Major, Eugene O (2013) Multiplex qPCR assay for ultra sensitive detection of JCV DNA with simultaneous identification of genotypes that discriminates non-virulent from virulent variants. J Clin Virol 57:243-8
Major, Eugene O; Frohman, Elliot; Douek, Daniel (2013) JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med 368:2240-1
Havla, J; Berthele, A; Kumpfel, T et al. (2013) Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab ""infusion group"". Mult Scler 19:1213-5
Matos, Ana; Duque, Vitor; Luxo, Cristina et al. (2012) Individuals infected with JC polyomavirus do not present detectable JC virus DNA in oropharyngeal fluids. J Gen Virol 93:692-7

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