Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central nervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circulation. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy-proven PML for the JCV genome. Two non-PML control groups, consisting of 26 patients seopositive for human immunodeficiency virus type 1 (HIV-1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was examined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV-1-seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD-1 strain of JCV in one patient with PML, a MAD-4 strain in a second patient with PML, and a slightly modified MAD-4 strain in an HIV-1-positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of Prolonged Survival in HLA-A2+ Progressive Multifocal Leukoencephalopathy Patients with a CTL Response Specific for a Commonly Recognized JC Virus Epitope

“…JCV is rarely found in the peripheral blood of normal persons (19,(21)(22)(23). JC viremia occurs in the setting of immunosuppression, and JCV DNA has been detected in the blood of HIV ϩ patients with or without PML who have CD4 ϩ cell counts below 200/l (19, 21, 24 -26).…”

Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS

“…Although JCV isolated from urine and kidney has almost exclusively been reported as archetype, the Mad-7 repeat structure was isolated from virus in the urine of a PML patient [80] and unpublished data from our laboratory show JCV repeat structure in the kidney of another PML patient. In many cases, lymphocytes from the peripheral blood of individuals with [75] and without [75][76][77] PML contain JCV with regulatory region repeat structures. A study using restriction enzyme digestion patterns in place of sequencing data, however, has demonstrated the presence of repeat and archetypelike structures in PBL [98].…”

“…Later studies applied polymerase chain reaction (PCR) amplification of unique viral nucleotide sequences to demonstrate JCV DNA in the circulating peripheral blood lymphocytes (PBL) of PML patients [75], non-PML immunocompromised patients [75,76], and other non-PML individuals [75,77]. The production of infectious JC virions was also detected in the B lymphocytic cell lines BJAB and Namalwa [7].…”

Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals

“…In addition to its productive replication in the brain, JCV particles have been isolated from the urine of PML patients as well as non-PML individuals who are experiencing mild to severe immunosuppression as well as in a large number of pregnant women Coleman et al, 1980;Gardner et al, 1984;Myers et al, 1989;Weiner et al, 1972). Viral sequences have also been demonstrated in kidneys and lymphocytes of healthy individuals leading to the speculation that these tissues may provide sites for JCV latency Dorries et al, 1994;Ishaq and Stoner, 1994;Matsushima et al, 1997;Tornatore et al, 1992;Vago et al, 1996;White et al, 1992). Of particular interest, in this respect, is the notion that the regulatory region of JCV from many of these healthy individuals is similar to that found in a Japanese urine isolate JCV(CY) (Yogo et al, 1990) and distinct from those originally obtained from PML brains.…”