ELEVATED Γ-Globulin AND INCREASED ANTIBODY PRODUCTION IN MICE INFECTED WITH LACTIC DEHYDROGENASE VIRUS

Abstract

Infection of mice with lactic dehydrogenase virus (LDV) resulted in a lifelong elevation of a number of plasma enzymes including lactic dehydrogenase, isocitric dehydrogenase, malic dehydrogenase, phosphohexose isomerase, and glutamic-oxaloacetic transaminase (1). Recent studies on the mechanism of enzyme elevation showed that infected mice cleared endogenous enzymes at a slower rate than uninfected mice (1). The present study was undertaken to see whether the catabolism of a "nonenzymatic" protein, T-globulin, was also altered. The experiments reported herein show that the catabolism of intlavenously administered I m ~'-globulin was not impaired in virus-infected mice, but that the level of endogenous 3,-globulin was elevated, and that the capacity of the infected mouse to produce antibody to a heterologous protein (human ~'-globulin) was enhanced. Materials and MethodsAnimals.--Except where indicated otherwise, conventional CAF-1 male mice, 4 to 6 wk old, obtained from the animal production section of the National Institutes of Health (NIH) were used throughout these experiments. Germfree male and female mice, 3 to 4 wk old, of the NIH stock colony were supplied by Dr. C. E. Miller of the Germfree Unit, Laboratory Aids Branch, and were housed in plastic isolators (2) in the Gnotobiotic Section of the National Institute of Dental Research. All materials introduced into the plastic isolators were treated so as to eliminate viable bacteria. To check for contamination, urine and feces were cultured twice a week.Virus.--The method of preparation and the assay for LDV have been described previously (3). Stock pools P-16 and P-17 were used throughout these experiments. The titer of the pools was approximately 10 l°.°IDs0/ml and all dilutions were made in Eagle's basal medium or 0.85% sodium chloride (saline). Mice were infected routinely with LDV by injecting intra-* Present address:

Effects of Tumour Cell Culture Supernatants on Some Biochemical Activities of Macrophages

“…The tumours appear to be free of lactic dehydrogenase virus, infection with which can alter host immune responsiveness (Notkins, 1971). Fibroblasts, provided by Dr. Y. Jnoue, had been obtained from trypsin-and pronase-digested subcutaneous tissue of anaesthetized rats by the method of Liotta et at.…”

The Murine Antibody Response to Lactate Dehydrogenase-elevating Virus

“…Lactate dehydrogenase-elevating virus (LDV) is a mouse virus, related to the togavirus family, that induces a life-long viraemia and considerable immunological alterations in adult mice (Riley et al, 1960;Notkins et al, 1966b;Howard et al, 1969;Michaelides & Simms, 1980;Coutelier & Van Snick, 1985). Infected mice have been found to produce significant amounts of anti-LDV antibodies, which form circulating immune complexes with the virus (Notkins et al, 1966a;Cafruny & Plagemann, 1982;McDonald et al, 1983).…”

Acute Infection of Mice with Lactate Dehydrogenase-elevating Virus Enhances Fc and Complement Receptor Activity of Peritoneal Macrophages

“…This acute infection is associated with the development of an impaired blood clearance of lactate dehydrogenase and some other enzymes which results in the plasma elevation of these enzymes (Rowson & Mahy, 1975). It is also associated with a transient enhancement of the humoral antibody response of infected mice to both T cell-dependent and -independent antigens (Michaelides & Simms, 1980;Notkins et al, 1966 a) and the depression of the cellular immune response (Howard et al, 1969;Michaelides & Schlesinger, 1974;Notkins, 1971;Turner et al, 1971). The acute infection invariably progresses into a life-long persistent infection which is characterized by a continuing elevation of plasma enzyme levels and a low-level viraemia (Notkins & Shochat, 1963;Rowson & Mahy, 1975).…”