Inhibition of hepatic phosphoenolpyruvate carboxykinase by avian reticuloendotheliosis viruses

Severe weight loss is associated with many malignant diseases of humans and animals. Avian reticuloendotheliosis viruses (RE viruses) induce runting in experimentally infected chickens. Chickens infected with a replication-competent RE virus, reticuloendotheliosis-associated virus, weighed 30-50% less than control birds at the time of death. Chickens infected with reticuloendotheliosis virus, a replication-defective acute leukemia virus, weighed 30% less than the controls. The runting induced by RE viruses does not occur because of reduced food intake. Activities of phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme in the liver, were reduced approximately 40 and 50%, respectively, by infection with reticuloendotheliosis-associated virus and reticuloendotheliosis virus. RE virus infection, however, did not affect the hepatic pyruvate carboxylase activity, indicating that inhibition of phosphoenolpyruvate carboxykinase is not due to a general inhibition of all liver enzymes. Birds given injections of UV-inactivated RE viruses or reticuloendotheliosis virus-transformed, non-virus-producing tumor cells also exhibited a reduction in phosphoenolpyruvate carboxykinase activity.