Fate of herpes simplex virus in lymphocytes from blood and joint effusions of systemic and pauciarticular juvenile chronic arthritis.

The fate of herpes simplex virus (HSV) in the lymphocytes of patients with juvenile chronic arthritis (JCA) was studied by previously described methods. Lymphocytes isolated from blood and joint effusions of 18 patients with systemic JCA and 11 patients with pauciarticular JCA usually supported viral growth normally.

Virus infections and chronic rheumatic disorders.

There is little direct evidence that viruses cause inflammatory arthritis in the sense that infectious agents classically cause disease. However, there are several mechanisms by which virus infections could be implicated in the pathogenesis of such disorders. In particular virus infection of lymphocytes could produce the combination of selective immunodeficiency and immune stimulation that characterizes many rheumatic disorders. In addition re-combination events between integrated pro-viruses in DNA and exogenous infections would account for the lack of any obvious correlation between the appearance of these disorders and any obvious preceding viral infection. Certainly, more sophisticated approaches will be needed to test such hypotheses rather than relying on classical techniques for viral isolation.

Lymphocyte abnormalities in Behçet's syndrome.

In order to test indirectly the hypothesis that Behçet's syndrome is caused by a virus, lymphocytes from eighty-six patients were evaluated for two parameters consistent with persistent virus infection: chromosomal abnormalities and decreased ability to herpes simplex virus type I (HSV) to grow in lymphocyte cultures stimulated by PHA. Whereas HSV grew in lymphocytes cultured from all normal donors, replication was impaired in lymphocytes from 37% of the patients with Behçet's syndrome. This figure is increased to 57% if patients receiving steroids or cytotoxic drugs were excluded. Lymphocytes were scored as chromosomally abnormal from sixteen of the thirty-eight patients examined, compared with only one of seventeen normal controls. There was damage to specific chromosomes in four patients. The frequency with which chromosomal abnormalities were detected was significantly related to failure to replicate HSV and inversely related to concomitant steroid treatment. The findings are consistent with a viral aetiology for Behçet's syndrome but other explanations are not excluded.

Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. ii. Mechanisms of non-permissiveness.

Mononuclear cells which were isolated from rheumatoid synovial effusions and cultured without prior separation failed to support the growth of herpes simplex virus (HSV). However, subpopulations of T lymphocytes separated on the basis of cell size or receptors for sheep red cells were, in isolation, permissive for this virus. Virus growth in these permissive cells was blocked by cocultivation with the remaining mononuclear cell populations.

Fate of herpes simplex virus in lymphocytes from inflammatory joint effusions. i. Failure of the virus to grow in cultured lymphocytes.

The ability of lymphocytes isolated from the blood and synovial effusions of patients with rheumatoid arthritis to support the growth of herpex simplex virus (HSV) was studied. Whereas blood lymphocytes supported virus growth, effusion lymphocytes were usually non-permissive. Lymphocytes obtained from the effusions of patients with other forms of inflammatory arthritis or suspected viral arthritis commonly failed to support the growth of HSV, but the virus grew in effusion lymphocytes from patients with noninflammatory joint disease. Several nonspecific factors which might have accounted for this non-permissiveness were excluded.