ABSTRACT JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML.

Two polyomaviruses, JC virus (JCV) and BK virus (BKV), affect humans. JCV is the causative agent of progressive multifocal leukoencephalopathy (PML), and detection of JCV in the central nervous system (CNS) is a prerequisite for confirmation of the disease. BKV is generally not associated with neurological disease, but involvement of BKV in patients with CNS disorders has been reported. In the present study polyomavirus DNA was detected by a nested PCR at a sensitivity corresponding to the detection of 10 copies of JCV DNA in 10 microliters of cerebrospinal fluid (CSF). CSF samples from 212 patients with neurological symptoms and immunodeficiencies were investigated for the presence of polyomavirus DNA. Of 128 human immunodeficiency virus (HIV)-infected patients, 14 (11%) had JCV DNA in their CSF, and all 14 patients had clinical PML. BKV DNA was detected in one HIV-infected patient with neurological symptoms not compatible with PML. Among 84 HIV-negative patients, 6 (7%) had detectable JCV DNA in their CSF, confirming PML in patients with clinical conditions of T-cell lymphoma, chronic lymphatic leukemia, status postliver transplantation, congenital immunodeficiency, sarcoidosis, and immunodeficiency of unknown origin. The specificity of the PCR was confirmed by a clinical follow-up study which showed full agreement between the detection of JCV DNA in CSF and clinically manifest PML. The described PCR is a rapid, reproducible, and easily performed assay.

In BMT patients, shedding of BK virus (BKV) in the urine has been strongly but not absolutely correlated to hemorrhagic cystitis (HC). The possible presence of human polyomaviruses in peripheral blood leukocytes (PBLs), plasma, serum and urine in BMT patients and an association with HC was investigated by a nested PCR assay. Samples from allogeneic BMT patients with and without HC as well as from autologous BMT patients were analyzed. Human polyomaviruses were detected in urine and blood samples of both allogeneic and autologous BMT patients with and without HC. An association between the presence of a specific human polyomavirus in blood and HC was thus not observed.

Polyomavirus‐infected oligodendrocytes and in some instances virus‐carrying macrophages were demonstrated within the cytoplasm of astrocytes by double immunostaining of brain lesions in a case of PML following bone marrow transplantation. The infected oligodendrocytes and CD68+ cells were usually partially or completely invested by the cytoplasm of reactive and infected or noninfected giant pleomorphic astrocytes. By electron microscopy (EM), internalized infected oligodendrocytes were shown to release polyomavirus particles possibly infectious to the astrocytes. These observations seem to indicate that astrocytes in PML can become infected by direct contact with internalized infected oligodendrocytes and possibly also by virus‐loaded macrophages. Correspondingly, astrocyte/oligodendrocyte/macrophage cell‐to‐cell interactions appear to play an important role in the pathogenesis of PML lesions.

Summary. Human T lymphotrophic virus type 1 (HTLV‐I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T‐cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV‐I negative identical sibling donor. During follow‐up after bone marrow transplantation, HTLV‐I could be repeatedly isolated inspite of anti‐viral prophylaxis. The patient died of an acute encephalitis and HTLV‐I could be detected in autopsy material from the brain. By a PCR‐based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T‐cell leukaemia.

BK and JC viruses are two polyoma viruses designated by the initials of the patients from whom they were first isolated. After the primary infection, usually occurring in childhood or early school age, the viruses become latent. Reactivation occurs during immunosuppression, and the BK virus has been shown to be the main cause of viral hemorrhagic cystitis in bone marrow transplanted patients, while the JC virus has been found to cause progressive multifocal leukoencephalopathy, PML. The paper consists in a report of results obtained with an established method for the amplification of BK and JC virus DNA. Of 20 urine specimens from patients with hemorrhagic cystitis, 13 were found to be BK virus-positive. Post-transplantation follow-up shows that the virus continues to remain detectable for long periods. JC virus positivity was found in central nervous system material (a cerebrospinal spinal fluid specimen in one case) from two PML patients.

Healy