VIRUS-INDUCED DIABETES MELLITUS : I. HYPERGLYCEMIA AND HYPOINSULINEMIA IN MICE INFECTED WITH ENCEPHALOMYOCARDITIS VIRUS

Infection of DBA/2N male mice with encephalomyocarditis virus resulted in a diabeteslike syndrome characterized by hyperglycemia, glycosuria, hypoinsulinemia, polydipsia, and polyphagia. Blood glucose levels were elevated within 4 days after infection and reached a maximum mean level of 320 mg/100 ml within 12 days. Approximately 60–80% of the animals developed a transient hyperglycemia while 10–15% of the animals remained hyperglycemic for well over 6 mo. The remaining animals failed to become hyperglycemic but many had abnormal glucose tolerance curves. Hyperglycemia was most pronounced when animals were allowed free access to food, and the incidence of byperglycemia was related both to the strain and sex of the animals, with few females developing hyperglycemia. The amount of immunoreactive insulin in the plasma of infected hyperglycemic mice was significantly lower than in appropriate controls, and injection of exogenous insulin resulted in a rapid drop in the blood glucose levels. Despite the fact that certain animals were hyperglycemic for many months, virus could not be recovered from the pancreas after the first 10 days of the infection

INFECTIOUS VIRUS-ANTIBODY COMPLEX IN THE BLOOD OF CHRONICALLY INFECTED MICE

If viremic sera from mice chronically infected with lactic dehydrogenase virus (LDV) were first treated with ether or ultraviolet light to inactivate the infectious virus, neutralizing antibody could be demonstrated. Significant amounts of antibody, however, were not detected until the mice had been infected for about 2½ months and its presence did not result in the elimination of the chronic viremia. Virus isolated from sera containing neutralizing antibody was found to be relatively resistant to neutralization by anti-LDV. Further studies revealed that the resistant virus existed in the form of an infectious virus-antibody complex (sensitized virus). The presence of such a complex was demonstrated by the fact that the virus fraction which persisted after in vivo or in vitro exposure to mouse anti-LDV was readily neutralized by goat anti-mouse sera or goat anti-mouse γ-globulin, whereas virus that had not been previously exposed to mouse anti-LDV was completely resistant to neutralization by goat anti-mouse sera. These findings suggest that (a) sensitization may play an important role in the resistance and susceptibility of a virus to neutralization by antiviral antibody, and (b) an anti-γ-globulin may prove useful in neutralizing the resistant fraction and in demonstrating otherwise undetectable antiviral antibody

MULTIPLE ENZYME CHANGES IN THE PLASMA OF NORMAL AND TUMOR-BEARING MICE FOLLOWING INFECTION WITH THE LACTIC DEHYDROGENASE AGENT

Within 72 hours after injection of the LDH agent into normal mice, five (LDH, ICDH, MDH, PHI, and GOT) out of the seven plasma enzymes studied were elevated. This elevation persisted for the duration of the experiment. Alkaline phosphatase and aldolase were not elevated. Plasma from mice bearing tumor SS-70429 and infected with the LDH agent showed 7 times more LDH, 8 times more ICDH, and 4 times more MDH activity than the plasma from mice with the same tumor but uninfected. The plasma aldolase activity from the infected tumor-bearing animal was approximately the same as that from the uninfected tumor-bearing animal. Somewhat similar results, but lower in magnitude, were found with mice bearing mammary carcinoma C3HBA. The early rise in plasma enzyme activity (LDH, MDH, ICDH) prior to the actual appearance of the tumor was shown to be due not to the tumor, but to the LDH agent. Uninfected tumor-bearing mice showed a late increase in plasma enzyme activity which appeared to be related to tumor growth. The findings reported above suggest that contamination with the LDH agent may have been responsible for much of the increased plasma enzyme activity previously attributed to the tumor