JC Virus - PML

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Demyelinating lesions in an immunocompromised patient

Laboratory Testing

  • Cerebrospinal fluid (CSF) testing – useful to exclude other more common diagnoses (eg, meningitis, encephalitis)
    • Should include cell count with differential, protein, glucose, and culture
    • PCR testing – positive test with appropriate clinical symptoms strongly supports diagnosis
      • May obviate need for brain biopsy
      • Negative test does not rule out PML


  • Brain biopsy – usually diagnostic; most useful if JC virus (JCV) not detected in CSF
    • May not be able to perform biopsy on debilitated patients
    • Key histologic features
      • Multifocal demyelination
      • Enlarged oligodendrocytes with nuclear inclusions
      • Large, bizarre astrocytes, reactive gliosis
        • Unusual astrocytes may cause confusion with glioma on biopsy
      • Minimal inflammation
  • Immunohistochemistry – JCV staining in oligodendrial cells and astrocytes

Imaging Studies

  • CT – patchy or confluent hypodense lesions in CNS white matter
  • MRI – more sensitive than CT
    • Recommended initial scan if suspicion for PML 
    • Hyperintense subcortical white matter lesions on T2-weighted images
  • Lesions do not have an anatomic predisposition

Differential Diagnosis

JC virus (JCV) is a human neurotropic polyomavirus that is the etiologic agent of progressive multifocal leukoencephalopathy (PML). PML is a rare, fatal, demyelinating disease of the central nervous system which almost always occurs in an immune-compromised setting.


  • Incidence 
    • ≥50% of population is JC virus infected 
    • PML presentation of the infection is rare
  • Age – all ages
  • Sex – M>F


  • JCV is a nonenveloped double-stranded DNA virus of the Polyomaviridae (formerly Papovaviridae) family, which also includes BK virus (BKV) and SV40
    • JCV infects only humans
    • JCV and BKV – named using the initials of the first patients identified with these diseases

Risk Factors

  • HIV infection
  • Use of immunomodulation therapy
    • Monoclonal antibodies
      • Natalizumab
      • Efalizumab
      • Alemtuzumab
      • Rituximab
      • Brentuximab
    • Mycophenolate mofetil
    • Malignancy (eg, leukemia, lymphoma)


  • Multifocal demyelination caused by lytic infection of the oligodendrocytes
    • Lesions range in size from 1 mm to several centimeters
    • Lesions may coalesce
    • Myelin loss may be extensive
    • Atrophy may occur

Clinical Presentation

  • Clinical presentation is diverse
  • Hemiplegia, visual disturbances, and subcortical dementia
    • Progressive – fatal within 3-6 months
  • Other symptoms – motor weakness, incoordination, gait abnormalities
  • May also have JC granule cell neuropathy, JC encephalopathy, JC meningitis
  • Found almost exclusively in patients with severe immune compromise
    • Considered an AIDS-defining illness – 85% of cases occur in this group
      • Usually occurs when CD4 count <200 cells/mm3
    • Also associated with lymphoproliferative disease, natalizumab therapy (Tysabri), rituximab

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

JC Virus by PCR 0099169
Method: Qualitative Polymerase Chain Reaction


Negative test does not rule out PML

Additional Tests Available

Cell Count, CSF 0095018
Method: Cell Count/Differential


Evaluate for bacterial versus viral etiology for CNS disorder

Findings not specific for JCV infections

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry


Evaluate protein level in suspected infectious meningitis/encephalitis

Findings not specific for JCV infections

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification


Confirm organism involved in CNS infection

Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008916
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay


Rule out other forms of encephalitis

Glucose, CSF 0020515
Method: Enzymatic


May be helpful in differentiating bacterial from viral etiology

Usually low (<10 mg/dL) in bacterial meningitis and tuberculous disease

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic


Quantifies glucose to match CSF glucose values


Berger J, Aksamit A, Clifford D, Davis L, Koralnik I, Sejvar J, Bartt R, Major E, Nath A. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013; 80(15): 1430-8. PubMed

General References

Berger J. Progressive multifocal leukoencephalopathy. Handb Clin Neurol. 2014; 123: 357-76. PubMed

Jiang M, Abend J, Johnson S, Imperiale M. The role of polyomaviruses in human disease. Virology. 2009; 384(2): 266-73. PubMed

Pinto M, Dobson S. BK and JC virus: a review. J Infect. 2014; 68 Suppl 1: S2-8. PubMed

Tan C, Koralnik I. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010; 9(4): 425-37. PubMed

Tyler K. Emerging viral infections of the central nervous system: part 2. Arch Neurol. 2009; 66(9): 1065-74. PubMed

Wang Y, Kirby J, Qian Q. Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy. J Med Microbiol. 2009; 58(Pt 2): 253-5. PubMed

Medical Reviewers

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Last Update: December 2015