Passage of Coxsackie virus (Connecticut-5 strain) in adult mice with production of pancreatic disease.

1. With Conn.-5 strain of Coxsackie virus, pancreatic disease can be regularly produced in adult mice. 2. The lesions consist of widespread necrosis, followed by repair; there occurs more or less complete loss of glandular acini, with fatty or fibrous replacement. The islands of Langerhans and pancreatic ducts persist. 3. Injection of virus suspensions by the intraperitoneal, subcutaneous, intramuscular, or intracerebral route is followed by selective necrosis of the pancreas. 4. The liver, in the earlier stages of the disease, is the seat of fat infiltration. There may be necrosis of individual hepatic cells, but the diffuse hepatitis described in suckling mice does not occur. In the later stages of the disease, the liver is not significantly altered. 5. Localized areas of fat necrosis, scattered through intra-abdominal adipose tissue, are usually present in the acute phase of the disease. These undergo fibrosis without calcification. 6. No lesions have been found in the skeletal muscle, even at the site of intramuscular injection. Central nervous system, heart, lungs, and peripheral fat lobules show no lesions comparable to those described in suckling mice. 7. Multiplication of virus takes place in the pancreas. Serial passage in adult mice, by injection of pancreas suspensions prepared from organs removed on the 4th day after infection, is readily accomplished. Five consecutive passages in adult mice have thus far been carried out. Pancreas suspension from 4th passage material produced typical disease in suckling mice when diluted 10(-6). No virus could be demonstrated in pancreas obtained 25 days after inoculation. 8. Complete protection against the pancreatic disease is obtained when the virus is neutralized, before injection, with Conn.-5 antiserum. Normal mouse serum and antiserum against the Ohio-R strain of Coxsackie virus have no protective effect. 9. Mice surviving the initial necrotizing effect of the virus, develop chronic pancreatic insufficiency. This is manifested by extreme weight loss-in some cases, 40 per cent or more of the body weight-and by hypoproteinemia, sometimes leading to anasarca. 10. The substitution of fox-chow which has been predigested with hog pancreas brings about a restoration of weight. 11. The possibility is considered that similar lesions of the pancreas in human beings may be due to virus infection.