Growth of measles virus in nervous tissues. III. Neurovirulence of SSPE virus in ferrets.

The Niigata-1 strain isolated from a patient with subacute sclerosing panencephalitis (SSPE) was inoculated intracerebrally into ferrets. Neurological signs developed in about 1 week in most of the animals. Histopathological examinations of the central nervous tissues revealed degenerative lesions in the parenchyma of the brains and inflammatory reactions predominantly in the meninges and choroid plexus. Virus antigen was demonstrated mainly in the nerve cells by immunofluorescent staining. The results indicated high affinity of the Niigata-1 strain to the nerve cells. In contrast, the Mantooth strain of SSPE virus in cell-free state did not exhibit neurovirulence in ferrets.     

Polyamines in encephalomyocarditis virus.

Encephalomyocarditis virus contains approximately 200 molecules of putrescine, 100 molecules of spermidine, and 40 molecules of spermine which could neutralize 11% of the viral genome. The same polyamines are present in different proportions in the Krebs ascites tumor cell in which the virus was grown.     

Susceptibility of chickens to avian encephalomyelitis virus. III. Behavior of the virus in growing chicks.

A chick embryo-adapted strain of avian encephalomyelitis virus was inoculated subcutaneously and orally into 40-day-old (middle-aged) and 110-day-old (advanced-aged) chicks to examine the behavior of the virus in the chick body. In the middle-aged chicks, the virus appeared in the muscle at the site of inoculation, liver, spleen, pancreas, lumbar and cervical portions of the spinal cord, and brain 1 approximately 9 days after subcutaneous inoculation, and remained mostly in the central nervous system up to 17 days after the inoculation. The virus was found in large amounts in the muscle at the site of inoculation (10(3.1)), lumbar portion (10(2.5)) and cervical portion (10(2.1)) of the spinal cord, brain (10(1.9)), and in minute amounts in the other organs examined. It appeared in 11 of 21 organs examined. In the middle-aged chicks inoculated by the oral route, the virus was detected transiently in small amounts from esophagus, pancreas, and rectum 4 approximately 14 days after inoculation. In the advanced-aged chicks inoculated by the subcutaneous route, the virus was detected in titer of 10(2.1) approximately 10(3.0) from the muscle at the site of inoculation 2 approximately 7 days after inoculation. The virus was also found sporadically in several organs up to 17 days after inoculation. In the advanced-aged chicks inoculated by the oral route, no virus appeared in any organ, but these chicks turned to be weakly positive for neutralizing antibody in the 4th or later week after inoculation.     

Susceptibility of chickens to avian encephalomyelitis virus. II. Behavior of the virus in day-old chicks.

The VR strain of avian encephalomyelitis virus, which had been adapted to embryonated hen's eggs, was inoculated into 2-day-old chicks by the subcutaneous route (10(2.5) approximately 10(3.0) EID50) or by the oral route (10(4.8) EID50). The chicks were examined chronologically for the distribution of the virus in the body. As a result, minute amounts of the virus were detected from the liver, spleen, pancreas, and muscle at the site of inoculation one day after inoculation and various amounts from almost all the organs 3 days and more after inoculation. The virus titer could nearly reach a maximum 7 to 9 days after inoculation. Above all, such high virus titers as ranging from 10(4.3) to 10(5.8) EID50/0.1 g were demonstrated in the brain, heart, liver, spleen, and pancreas. After that, there was a tendency for virus titer to decrease in most organs and for virus to multiply persistently in the pancreas, brain, and eyeball. Virus titer was maintained at a level of 10(2.3) approximately 10(2.8) EID50/0.1 g in these three organs even 21 days after inoculation. In the group of subcutaneous inoculation, all the chicks manifested clinical signs of infection 5 to 10 days after inoculation. On the other hand, no chicks were involved in clinical infection in the group of oral inoculation. Multiplication of the virus was delayed in the body of these chicks. Small amounts of the virus were detected from the spleen and pancreas 11 days after inoculation. Low titers (10(2.7) EID50/0.1 g at the highest) of the virus were only detected from the brain, spinal cord, spleen, pancreas, esophagus, and other organs 14 and 21 days after inoculation.     

Susceptibility of chickens to avian encephalomyelitis virus. IV. Behavior of the virus in laying hens.

Some laying hens 6 months of age were inoculated subcutaneously or orally with a chick embryo--adapted strain of avian encephalomyelitis virus and examined for propagation of the virus in the body. When inoculated subcutaneously, the virus appeared in liver, spleen, ovarian follicle, and muscle at the site of inoculation 1 day, in kidney and lumbar part of the spinal cord 3 days, in the pancreas 5 days, in heart, duodenum, and cervical part of the spinal cord 7 days, and in the brain 11 days after inoculation. After its appearance, it increased gradually in amount in liver, spleen, pancreas, muscle at the site of inoculation, and cervical and lumbar parts of the spinal cord, but remained at a low level in any other organ. When examined 14 days after inoculation and later, it was distributed mainly in the central nervous system. It was detected from 12 of 16 organs examined. The highest virus level in each organ was 10(2.6)/0.1 g in pancreas and lumbar part of the spinal cord, which were followed by muscle at the site of inoculation (10(2.0)/0.1 g), spleen (10(1.8)/0.1 g), cervical part of the spinal cord, heart, and liver in the order listed. When inoculated orally, the virus was found sporadically in spleen, pancreas, kidney, cecum, ovarian follicle, and lumbar part of the spinal cord. The virus level was low in these organs, of which pancreas, kidney, and lumbar part of the spinal cord showed the highest virus level, or 10(1.3)/0.1 g.     

Lymphocytic Choriomeningitis virus. I. Concentration and purification of the infectious virus.

Two procedures for the purification of infectious lymphocytic choriomeningitis virus from cell culture fluid have been developed. If large quantities of very pure virus are to be prepared, infected L cells are maintained with a medium supplemented with calf serum, the proteins of which have been largely removed by pretreatment with polyethylene glycol. Two days after infection of the cultures, the media are collected and the virus is concentrated by treatment with polyethylene glycol 40,000. Purification with a 10,000-fold increase of specific infectivity is achieved with steric chromatography on controlled-pore glass beads with pore sizes of 42 to 44 nm and centrifugation in density gradients prepared with amido trizoate. An alternative method begins with precipitation of the virus from infected cell cuture medium with zinc acetate, followed by controlled-pore glass chromatography and density centrifugation in a discontinuous sucrose gradient. Purification thus obtained is 200-fold in terms of specific infectivity.     

Hepatitis B virus in hepatocarcinogenesis.

Hepatitis B virus (HBV) is an important etiologic agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Although the mechanism whereby HBV causes HCC is not fully understood, it is likely that there are many relevant molecular pathways that contribute to the development of HBV-associated HCC. This review provides an overview of some of these proposed pathways and their relative importance. It also raises questions on basic and translational research that will signficantly contribute to the better understanding of underlying mechanisms, prevention, and treatment of this tumor type.