Research Topics
| I J KoralnikSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Metabolic profile of PML lesions in patients with and without IRIS: an observational studySarah Gheuens
Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Neurology 79:1041-8. 2012....- Detection of JC virus-specific cytotoxic T lymphocytes in healthy individualsR A Du Pasquier
Division of Viral Pathogenesis and Department of Neurology, Research East, Room 213B, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215
J Virol 78:10206-10. 2004..These results show that a CD8+-T-cell response against JCV is commonly found in immunocompetent people and suggest that these cells might protect against the development of PML... 
Progressive multifocal leukoencephalopathy revisited: Has the disease outgrown its name?Igor J Koralnik
HIV Neurology Center, Department of Neurology, and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Ann Neurol 60:162-73. 2006..Hopefully, this crisis will be instrumental in helping us define novel avenues of research, develop predictive tests for PML in populations at risk, and challenge us to find a treatment for this deadly disease...- New insights into progressive multifocal leukoencephalopathyIgor J Koralnik
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Curr Opin Neurol 17:365-70. 2004..This review covers recent developments in the clinical and pathological presentations of progressive multifocal leukoencephalopathy, and advances in the understanding of JC virus biology... - JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathyR A Du Pasquier
Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurovirol 7:318-22. 2001..As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression... - Determinants of survival in progressive multifocal leukoencephalopathyA Marzocchetti
Division of Viral Pathogenesis, BIDMC, Harvard Medical School, Boston, MA 02215, USA
Neurology 73:1551-8. 2009..We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with progressive multifocal leukoencephalopathy (PML)... - JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathyI J Koralnik
Department of Neurology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 75:3483-7. 2001..These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients... - Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathyM A Lima
Department of Neurology, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, MA 02215, USA
J Neurol Neurosurg Psychiatry 81:1288-91. 2010..In absence of a specific treatment, immunotherapies aiming at boosting the cellular immune response against JCV may improve the prognosis of PML... - Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patientF Bernal Cano
Department of Neurology, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
J Neurovirol 13:474-6. 2007..Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter... - A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathyRenaud A Du Pasquier
Division of ViralPathogenesis Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Brain 127:1970-8. 2004..Fluctuations of JCV-specific CTL in the blood are associated with variation in disease manifestations. These results indicate that JCV-specific CTL are associated with the control of PML... - JC virus regulatory region tandem repeats in plasma and central nervous system isolates correlate with poor clinical outcome in patients with progressive multifocal leukoencephalopathyL A Pfister
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 75:5672-6. 2001..These data suggest that the presence of tandem repeats in plasma and CNS JCV RR clones is associated with poor clinical outcome in patients with PML... - The spectrum of neurological disorders in a Zambian tertiary care hospitalOmar K Siddiqi
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
J Neurol Sci 290:1-5. 2010..To define the spectrum of inpatient and outpatient neurological illness in a Zambian tertiary care facility where HIV is endemic... - Elevation of myoinositol is associated with disease containment in progressive multifocal leukoencephalopathyRachel Katz-Brull
Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Neurology 63:897-900. 2004..Concomitantly, JC virus-specific cytotoxic T lymphocytes were only detected in the blood of PML survivors. These results suggest that inflammation limits disease progression... - Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathyIgor J Koralnik
Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Neurovirol 8:59-65. 2002..02). This cellular immune response may therefore be crucial in the prevention of PML disease progression and the tetramer staining assay may be used as a prognostic marker in the clinical management of these patients... - Low frequency of cytotoxic T lymphocytes against the novel HLA-A*0201-restricted JC virus epitope VP1(p36) in patients with proven or possible progressive multifocal leukoencephalopathyRenaud A Du Pasquier
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 77:11918-26. 2003..These data suggest that, although present in low numbers, JCV-specific CTL may be of central importance in the containment of JCV spread in immunosuppressed individuals... - Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitopeIgor J Koralnik
Neurology Department, Beth Israel Deaconess Medical Center, RE 213B, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215
J Immunol 168:499-504. 2002..These data suggest that the JCV-specific cellular immune response may be important in the containment of PML, and the tetramer-staining assay may provide a useful prognostic tool in the clinical management of these patients... - Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MSS Gheuens
Division of Neurovirology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Neurology 78:1390-3. 2012..We describe a patient with MS who presented with simultaneous PML-IRIS 2 months after stopping natalizumab for other reasons. CASE REPORT and.. - Remission of progressive multifocal leukoencephalopathy and primary central nervous system lymphoma in an HIV-infected patientM A Lima
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Eur J Neurol 14:598-602. 2007.... - Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individualR A Du Pasquier
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Neurology 61:775-82. 2003..CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals... - Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathyYiPing Chen
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Virol 80:3495-505. 2006..A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses... - New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumabMarco A Lima
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Neurovirol 11:52-7. 2005.... - A granule cell neuron-associated JC virus variant has a unique deletion in the VP1 geneXin Dang
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, RE 213C, 330 Brookline Avenue, Boston, MA 02215, USA
J Gen Virol 87:2533-7. 2006..This deletion was not present in JCV(HWM), suggesting that this mutation may be instrumental in facilitating entry or replication of JCV into granule cell neurons... - Frequent infection of cerebellar granule cell neurons by polyomavirus JC in progressive multifocal leukoencephalopathyChristian Wuthrich
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
J Neuropathol Exp Neurol 68:15-25. 2009..These results indicate that infection of GCNs is an important, previously overlooked, aspect of JCV pathogenesis in immunosuppressed individuals... - Lymphomatoid papulosis and human herpesviruses--A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 related herpesvirusesW Kempf
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
J Cutan Pathol 28:29-33. 2001..Ultrastructural and clinical features of LyP suggest that it has a viral etiology. Human herpesviruses have been proposed as causative cofactors for LyP because of their oncogenic potential and their association with other lymphomas... - BKV and JCV large T antigen-specific CD8+ T cell response in HLA A*0201+ kidney transplant recipients with polyomavirus nephropathy and patients with progressive multifocal leukoencephalopathyYiPing Chen
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Clin Virol 42:198-202. 2008..The large T-antigen (T-ag) is the main regulatory protein of polyomaviruses that is expressed early in the viral cycle... - JC virus induces a vigorous CD8+ cytotoxic T cell response in multiple sclerosis patientsRenaud A Du Pasquier
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA, USA
J Neuroimmunol 176:181-6. 2006..These findings may shed a new light on the recent events related to the development of progressive multifocal leukoencephalopathy in three natalizumab-treated patients... - Efficient in vitro expansion of JC virus-specific CD8(+) T-cell responses by JCV peptide-stimulated dendritic cells from patients with progressive multifocal leukoencephalopathyAngela Marzocchetti
Div of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, USA
Virology 383:173-7. 2009..JCV peptide-loaded DC elicited a stronger CTL expansion in 13/15 responders. DC can induce a potent JCV-specific CTL response in vitro, and may constitute a promising approach for PML immunotherapy... - JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathyIgor J Koralnik
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Ann Neurol 57:576-80. 2005..We propose to call this novel syndrome JCV granule cell neuronopathy (JCV GCN)... - Role of human leukocyte antigen class I alleles in progressive multifocal leukoencephalopathySarah Gheuens
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, E CLS 1005, 330 Brookline Avenue, Boston, MA 02215, USA
J Neurovirol 16:41-7. 2010..Physicians may exercise caution in the use of immunomodulatory medications in patients whose genetic background is associated with an increased risk of PML... - BK virus-associated hemorrhagic cystitis in a Human Immunodeficiency Virus-infected patientDan H Barouch
Division of Infectious Diseases, Massachusetts General Hospital, and Division of Infectious Diseases, Brigham and Women s Hospital, Boston, MA, USA
Clin Infect Dis 35:326-9. 2002.... - Asymptomatic reactivation of JC virus in patients treated with natalizumabYiPing Chen
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA
N Engl J Med 361:1067-74. 2009..Most adults who are infected with the JC virus, the etiologic agent in PML, do not have symptoms. We sought to determine whether exposure to natalizumab causes subclinical reactivation and neurotropic transformation of JC virus... - Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathyAngela Marzocchetti
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurovirol 14:455-8. 2008..Further studies will be needed to determine the prevalence of JCV in bone marrow of immunosuppressed individuals at risk of PML and characterize the RR and phenotype of these JCV isolates... - Progressive multifocal leukoencephalopathy in a patient with relapsed acute myelogenous leukemiaSantosh Kesari
Department of Neurology, Dana-Farber/Brigham and Women's Cancer Center, Center for Neuro-Oncology, Boston, MA, USA
J Clin Oncol 26:3804-7. 2008 - Productive simian virus 40 infection of neurons in immunosuppressed Rhesus monkeysXin Dang
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Neuropathol Exp Neurol 67:784-92. 2008..These findings shed new light on SV40 neurotropism and expand the host cell range of this virus... - Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neuronsChristian Wuthrich
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Ann Neurol 65:742-8. 2009..This novel gray matter syndrome expands the scope of JCV clinical presentation and pathogenesis... - Inflammatory reaction in progressive multifocal leukoencephalopathy: harmful or beneficial?Renaud A Du Pasquier
Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurovirol 9:25-31. 2003..Therefore clinicians should not disregard the diagnosis of PML in presence of contrast-enhancing brain lesions, and should use caution before treating these immunosuppressed individuals with steroids... - Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesisChen S Tan
Division of Viral Pathogenesis, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Lancet Neurol 9:425-37. 2010..The increasingly diverse populations at risk and the recent discovery of the presence of the JC virus in the grey matter invite us to reappraise the pathogenesis of this virus in the CNS... - Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathyMarco A Lima
Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
J Virol 81:3361-8. 2007..Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML... - Atypical radiological presentation of progressive multifocal leukoencephalopathy following liver transplantationMarco A Lima
Department of Neurology, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Neurovirol 11:46-50. 2005..The authors report an atypical presentation of PML with contrast-enhancing lesions and mass effect on the MRI in a liver transplant recipient,who had a progressive course and fatal outcome... - Characterization of lymphocytic infiltrates in progressive multifocal leukoencephalopathy: co-localization of CD8(+) T cells with JCV-infected glial cellsChristian Wuthrich
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurovirol 12:116-28. 2006..These observations are discussed in the context of the recent evidence of PML in multiple sclerosis and Crohn's patients treated with natalizumab, underscoring the role of CD8(+) T lymphocytes in continued immunosurveillance of the CNS... - Rearrangement of simian virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed rhesus monkeysXin Dang
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-213, 330 Brookline Ave, Boston, MA 02215, USA
J Virol 79:1361-6. 2005..These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys... - Seizures and their outcome in progressive multifocal leukoencephalopathyMarco A Lima
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Neurology 66:262-4. 2006..Seizures usually responded well to treatment and did not affect survival. The presence of PML lesions immediately adjacent to the hemispheric cortex was the only risk factor associated with seizures in this population... - Role of CD4+ and CD8+ T-cell responses against JC virus in the outcome of patients with progressive multifocal leukoencephalopathy (PML) and PML with immune reconstitution inflammatory syndromeSarah Gheuens
Division of Neurovirology, Beth Israel Deaconess Medical Center, E CLS 1005, 330 Brookline Avenue, Boston, MA 02215, USA
J Virol 85:7256-63. 2011..ELISpot and ICS assays are useful prognostic markers of PML evolution and may help in the clinical management of these patients... - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14-2004. A 66-year-old man with progressive neurologic deficitsIgor J Koralnik
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, USA
N Engl J Med 350:1882-93. 2004 - Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequencesJohn Y H Kim
Division of Neuroscience, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Neuro Oncol 4:165-70. 2002..In contrast to childhood ependymomas and choroid plexus tumors, medulloblastomas and sPNETs infrequently express evidence of polyomavirus infection... - Mirtazapine in progressive multifocal leukoencephalopathy associated with polycythemia veraSusama Verma
Department of Neurology, Mount Sinai Medical Center, New York, NY 10029, USA
J Infect Dis 196:709-11. 2007..We propose that mirtazapine should be investigated further for use in PML... - Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppressionSarah Gheuens
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
J Neurol Neurosurg Psychiatry 81:247-54. 2010..The authors performed a review of the literature to find similar cases... - Analysis of 15 novel full-length BK virus sequences from three individuals: evidence of a high intra-strain genetic diversityYiPing Chen
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, RE 213B, 330 Brookline Avenue, Boston, MA 02215, USA
J Gen Virol 85:2651-63. 2004..55 % of sites, implying a rate of nucleotide substitution of approximately 5 x 10(-5) substitutions per site per year, which is two orders of magnitude faster than estimated for the other human polyomavirus, JC virus... - Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformationChen S Tan
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Infect Dis 199:881-8. 2009.... - Endogenous retroviral elements, but not exogenous retroviruses, are detected in CD30-positive lymphoproliferative disorders of the skinWerner Kempf
Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Carcinogenesis 24:301-6. 2003 - JC virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathyChen S Tan
Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
J Virol 84:9200-9. 2010..These results provide evidence of JCV latency in the brain prior to severe immunosuppression and suggest new paradigms in JCV latency, compartmentalization, and reactivation... - Presence of JC virus-specific CTL in the cerebrospinal fluid of PML patients: rationale for immune-based therapeutic strategiesRenaud A Du Pasquier
Division of Viral Pathogenesis and Beth Israel Deaconess Medical Center, Boston Massachusetts 02215, USA
AIDS 19:2069-76. 2005..The breadth of the TCR repertoire was CTL epitope dependent. CONCLUSIONS: These results indicate that JCV-specific CTL are present in the CNS of PML patients and pave the way for an immune-based therapeutic approach... - The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: defining a consensus terminologyPaola Cinque
Clinic of Infectious Diseases, San Raffaele Hospital, Milano, Italy
J Neurovirol 9:88-92. 2003..A standard patient classification would be helpful for clinical management of PML patients, for their inclusion in clinical studies, and also will increase our current knowledge of PML and its evolution in relation with HAART... - Progressive multifocal leukoencephalopathy and natalizumab--unforeseen consequencesJoseph R Berger
N Engl J Med 353:414-6. 2005 - Progressive multifocal leukoencephalopathy as a complication of hepatitis C virus treatment in an HIV-negative patientMarco A Lima
Clin Infect Dis 41:417-9. 2005 - Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeysMichael K Axthelm
Vaccine and Gene Therapy Institute, Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA
J Neuropathol Exp Neurol 63:750-8. 2004..This observation suggests that a primary polyomavirus infection can be associated with an inflammatory CNS process. These data shed new light on the pathogenic mechanisms of primate polyomaviruses in the immunocompromised host...
Research Grants
- Role of Inflammation in Progressive Multifocal LeukoencephalopathyIgor J Koralnik; Fiscal Year: 2010..The knowledge we will gain from these studies will greatly expand our understanding of JCV pathogenesis and will have a direct impact on patient care. ..
- Cellular Immunity/JC Virus/AIDS/LeukoencephalopathyIgor Koralnik; Fiscal Year: 2007..class I alleles in PML outcome 2) Characterize the phenotype of JCV-specific CTL 3) Analyze the repertoire of JCV-specific CTL in blood and CSF 4) Perform preclinical studies of dendritic cell-based immunotherapy for PML ..
- Cellular Immunity/JC Virus/AIDS/LeukoencephalopathyIgor Koralnik; Fiscal Year: 2009....
- Role of Inflammation in Progressive Multifocal LeukoencephalopathyIgor Koralnik; Fiscal Year: 2009..The knowledge we will gain from these studies will greatly expand our understanding of JCV pathogenesis and will have a direct impact on patient care. ..
- Inflammation in Progressive Multifocal LeukoencephalopathyIgor Koralnik; Fiscal Year: 2007..abstract_text> ..
- CELLULAR IMMUNITY TO JC VIRUS IN AIDS ASSOCIATED PMLIgor Koralnik; Fiscal Year: 2004..complex staining and ELISPOT assays 6) define the cellular immune response to JCV in the cerebrospinal fluid 7) correlate the detection of JCV-specific CTL with the immune status and clinical course of patients with PML ..
- AIDS-assoc Progressive Multifocal LeukoencephalopathyIgor Koralnik; Fiscal Year: 2004..We expect that these hybrid viruses will produce a disease more closely resembling PML. The availability of an animal model of PML will allow new therapeutic interventions for this incurable disease. ..
- Granule cell neuron-tropic JC virus variantIgor Koralnik; Fiscal Year: 2006....