A new virus of minimal pathogenicity associated with Friend virus. II. Histological changes and immunodepressive effect.
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Biomedical subjects
Publications and source records attributed to K E Rowson.
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The plasma clearance of intravenously injected rabbit muscle LDH was studied. In normal mice the clearance followed a biphasic exponential curve comprising an initial fast and subsequent slow phase. Riley virus-infected mice showed only the slow phase of enzyme clearance. The change from fast to slow clearance rate in normal mice appeared to depend upon the level of plasma enzyme activity rather than on the amount of enzyme cleared. Treatment of mice with RES-blocking agents (cholesterol oleate and carbon) inhibited the fast clearance phase, whereas an RES-stimulating agent (stilbestrol) caused an accelerated rate of enzyme clearance. Riley virus infection was found to inhibit the clearance of phosphoglucose isomerase, but had no effect on the clearance of alanine transaminase. The activity of the former enzyme is raised in the plasma of infected mice, whereas the activity of the latter enzyme is unaltered.
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Plasma LDH levels were determined in normal and Riley virus-infected mice following treatment with various drugs known to alter the activity of the RES. The rise in plasma LDH level after Riley virus infection was considerably enhanced by previous treatment with thorotrast (to produce blockade of the RES), and decreased by previous treatment with stilboestrol (to stimulate the RES). A dose of 2000 r whole-body x-irradiation, lethal within 3 to 4 days, did not alter the phagocytic activity of the RES, and was without effect on plasma LDH activity in normal mice, or on the rise in plasma LDH level following infection with Riley virus. Blockade of the RES with cholesterol oleate, thorotrast, or zymosan, resulted in a 2- to 3-fold rise in plasma LDH level within a few hours. The level returned to normal by 1 to 3 days. Stimulation of the RES with stilboestrol resulted in a decrease in plasma LDH level by 1 to 2 days in both normal and infected mice, with a return to normal by about a week. Blockade of the RES in uninfected mice with thorotrast or cholesterol oleate, besides increasing the plasma LDH level caused a rise in plasma phosphoglucose isomerase level, but no significant alterations in plasma aldolase or alanine transaminase levels, studied up to 10 days. Riley virus causes a similar pattern of enzyme elevation. It is suggested that the increased levels of certain plasma enzymes in Riley virus-infected mice may be due to competitive inhibition by virus particles of plasma enzyme clearance by the RES.
The level of viraemia was determined in serial blood samples obtained from 2 mice after the injection of Riley virus. The plasma virus titre rose rapidly to a peak value of 10(9) to 10(10)ID(50) per ml by 24 hours after infection, and then fell slowly to a level of 10(5) to 10(6)ID(50) per ml by the 10th day after infection, where it remained relatively stable. Neither blockade of the RES with thorotrast, zymosan, or carbon, nor stimulation of the RES with stilboestrol or zymosan, before the injection of Riley virus, produced any observable alteration in the level of viraemia attained 24 hours after infection. However 10 days or more after infection with Riley virus blockade of the RES with thorotrast caused a transitory rise, and stimulation of the RES with stilboestrol caused a slight but prolonged fall, in the level of viraemia. Zymosan injection at this period of infection caused an initial rise, followed by a fall, in the level of viraemia; these changes correlated with the initial period of blockade and the subsequent period of stimulation of the RES observed in carbon clearance studies. The clearance of injected Riley virus particles from the plasma over a period of 3 hours after injection was measured in previously uninfected mice and mice which had been infected with Riley virus for 3 weeks. The mice which had been infected 3 weeks before the test cleared rather more of the injected virus than the previously uninfected mice. It is concluded that although the activity of the RES affects, and may determine, the level of viraemia, the permanence of the viraemia in Riley virus-infected mice does not appear to be due to a failure of the RES to clear virus particles from the plasma.