Brian G.M. Durie, Russell A. Collins, W. John Martin Cancer Center, Cedars Sinai Medical Center, Los Angeles, CA, USA; Center for Complex Infectious Diseases, Rosemead, CA, USA

We have used viral culture techniques to screen patients with multiple myeloma for the presence of stealth-adapted viruses: a newly defined grouping of atypically-structured, poorly immunogenic viruses which induce a characteristic vacuolating cytopathic effect (CPE) in human and animal cell lines. Electron microscopy, serology and molecular-based assays have been used to further differentiate stealth-adapted viruses from conventional cytopathic viruses. Peripheral blood mononuclear cells from 20 patients with multiple myeloma were added to human MRC-5 fibroblasts. All cultures showed unequivocal, extensive foamy syncytial cell formation. Mononuclear cells from 10 patients were re-tested in a blinded fashion along with 10 samples obtained randomly from hospital outpatients. Nine of the 10 myeloma patient samples rapidly gave strong positives; the 10th became positive with serial observation, whereas no (zero) controls became positive. Positive cultures have also been obtained from bone marrow, CSF and pleural fluid of myeloma patients. Stealth viral infections have previously been linked to encephalopathy with complex and diverse neuropsychiatric manifestations. Detailed clinical review of the tested myeloma patients revealed neurologic abnormalities in 4 patients (brain and meningeal plamacytomata, facial myoclonic seizures and nerve deafness), and prior neuropsychiatric abnormalities in a further 9 patients (ranging from emotional/cognitive difficulties to chronic fatigue syndrome). Since stealth virus replication can lead to varying re-combinations of mutated viral and cellular genetic sequences, virus assimilation and over-expression of genes coding myeloma growth factors could enable a stealth-adapted virus to promote the development of myeloma. Assessment of this will require sequence comparisons of stealth viruses from patients with and without myeloma. Our observations warrant these and other studies to clarify the significance of positive stealth virus cultures in myeloma patients.

Keywords: Multiple myeloma; Stealth virus