Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs.

Progressive Multifocal Leukoencephalopathy after Natalizumab Therapy for Crohn's Disease

“…Polyomavirus infection is widespread, and antibodies are detected in serum in 50 to 85 percent of persons in the United States and Europe. 12 After primary infection, the virus resides in the kidney, 13 and it is not entirely clear how the virus is transported to the brain. It is assumed that B cells deliver the virus to the oligodendrocytes, but active replication does not appear to occur in the blood.…”

JC Virus T-Antigen DNA in Gastrointestinal Mucosa of Immunosuppressed Patients: A Prospective, Controlled Study

“…One case of PML associated with natalizumab in refractory Crohn's disease has been reported [19]. The precise mechanism of reactivation of the virus is not completely clear, nor is the pathway by which the virus reaches the brain [20].…”

Immunoglobulin G, A, and M Responses to BK Virus in Renal Transplantation

“…In patients with AIDS, JCV causes progressive multifocal leukoencephalopathy. Using PCR, JCV DNA can be amplified in up to 75% of blood samples and 92% of cerebrospinal fluid samples obtained from patients with progressive multifocal leukoencephalopathy and systemic lupus erythematosus (15,18,39,54). Viral DNA has also been documented in human neoplasms, including brain tumors and carcinoma of the colon, and nephrectomy specimens with renal cell carcinoma (33).…”