Absence of measles proviral DNA in systemic lupus erythematosus.

Abstract

MEASLES VIRUS usually causes an acute self-limiting infection in humans and a productive cytolytic infection in susceptible tissue culture cells. However, measles-like virus has been isolated from the brains of patients with subacute sclerosing panencephalitis (SSPE), a chronic progressive neurological disorder of children1. Also, persistent measles infection has been implicated in the pathogenesis of several chronic diseases of unknown aetiology, including multiple sclerosis2 and systemic lupus erythematosus (SLE)3. Manipulation of the conditions of infection can result in persistently infected tissue culture cells, which have been proposed as a model system for studying the molecular mechanisms responsible for cytolytic virus persistence in man4–6. There is experimental evidence for at least four mechanisms leading to the induction of persistent measles infections: the production of defective virus particles which interfere with the replication of complete virus7, the generation of mutant virus strains with the capacity for non-cytolytic replication8, and infection of certain cell types (for example, neurones) restricted in their capacity to support all steps in virus replication9. Zhdanov et al.10–13 have proposed that measles virus persists in cells by a mechanism similar to that shown for retroviruses, that is, the synthesis of a DNA copy of the viral genome and the insertion of the proviral DNA into the host cell chromosome. This would be a novel mode of replication, as the replication of measles virus in cytolytic infections involves a double-stranded RNA intermediate. Using tritium-labelled viral RNA probes in molecular hybridisation assays, Zhdanov et al. have demonstrated the presence of measles virus-related DNA in chick embryo cells11 and human lymphoid cells13 persistently infected with measles virus. Further, they detected measles virus-related DNA in leukocytes, lymph nodes, kidney and urine cell sediment from five SLE patients12. Negative results were obtained using cells from appropriate control tissues. The obligative reverse transcriptase was found in the persistently infected cell lines and SLE tissues, and concomitant retrovirus infection was proposed as a prerequisite for persistent measles infection. Thus, these studies not only provide insights into the molecular mechanisms of measles virus persistence but suggest aetiological relationships for a fatal disease of unknown cause. However, we report here that, using a more sensitive nucleic acid hybridisation assay, we were unable to confirm the presence of measles virus-related DNA in either persistently infected cells or cells from patients with SLE.