Abstract
Discussion and Summary
The results presented show that treatment of bats with either endotoxin or 6-thioguanine prior to inoculation with JBE or SLE virus affects the course of infection in these animals. At a given harvest time, when little virus was demonstrable in the tissues of control animals, tissues from most bats pretreated with either substance showed evidence of viral multiplication. This increase in susceptibility was much more marked in bats maintained at 24° than in those held at 37° where, in some instances, no change in the response to virus was observed. The apparent difference in the effect of these two substances on experimental arbovirus infection in bats maintained at 24° versus animals held at 37° could possibly be due to variations in the metabolism of the compounds at the different temperatures. Although treatment with endotoxin or thioguanine increased the multiplication of JBE and SLE virus in various tissues of the bat, no overt signs of encephalitis were observed in any of the treated animals during the course of the experiments.
Both 6-thioguanine and endotoxin are believed to influence the susceptibility of animals to bacterial and viral infections through action on the reticuloendothelial system. As already mentioned, 6-thioguanine is a radio-mimetic compound and, hence, has effects similar to those of X-rays which are known to injure the phagocytic mechanism (7, 8). Although macrophages from X-rayed animals are still capable of ingesting infectious agents (9-11), the power to destroy the agents is lost and multiplication within the phagocytic cells can occur, furthering the infection (12, 13). Mims' suggestions concerning the role of macrophages in viral pathogenesis (14, 15) are important in light of the above mentioned observations. If macrophages are made to support multiplication of a virus which they would otherwise destroy, a successful infection may be established where it could not be normally. Endotoxin also affects the reticuloendothelial system (4) but the nature of the effect is more complicated. A single large dose of endotoxin reduces the ability of the macrophages to ingest whereas several doses cause first an inhibition then a stimulation of the reticuloendothelial system (16). Another factor in the effect of endotoxin is the presence of a pyrogenic substance which could have affected the response of the bat to virus at the different environmental temperatures.
Regardless of the exact mechanism of the effects of endotoxin and thioguanine, both do affect the reticuloendothelial system and the response of the bat to experimental infection with JBE or SLE virus. It may be inferred, then, that the success of viral infections in the bat, as in the mouse, may depend to a great extent on the response of the reticuloendothelial system to the agent. Results obtained in studies concerned with early sites of multiplication of JBE and SLE virus in experimentally infected bats (Middle-brooks, et al., unpublished observations) support this hypothesis. It was found that the liver rapidly removed injected virus from the blood and that this organ was a prime site for viral multiplication. In all cases virus apparently multiplied originally in the vascular endothelium and macrophages.
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