In vitro and in vivo studies of coxsackievirus B3-induced hepatitis

• Main Authors: Jung-Yen Liu, 劉蓉燕
• Other Authors: Ching-Chuan Liu
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/28967670246735121577

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 94 === Coxsackievirus B (CB) belongs to the Picornaviridae family. It is responsible for an array of clinical diseases ranging from asymptomatic illness to severe diseases such as myocarditis, meningoencephalitis and fulminant hepatitis. In 2005 an outbreak of CB infection, which was characterized by fulminant hepatitis in neonates occurred in Taiwan. Patients with CB-associated fulminant hepatitis usually have abnormal liver function with markedly elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Using clinical isolated strains, we found that CB3 grew in hepatocytes and induced cell death more severe than other enteroviruses. These observations also could be demonstrated in seven-day-old ICR mice. After intraperitioneal inoculation, CB3 was first detected in the liver. At the 48 hours post infection, virus could be isolated from many tissues, including brain, heart, lung, liver and spleen, with liver being the organ containing the highest viral titer. Histopathological studies illustrated neutrophilic infiltration and cell death in the liver. Furthermore, we found that decay accelerating factor (DAF), a CB receptor, was up-regulated on PBMC of CB patients. To exploit the possible mechanisms of CB3 entry, we examined the expression of the viral receptors in various mice organs. We found that coxsackievirus-adenovirus receptor (CAR) was highly expressed in the liver of newborn mice, and the expression was inversely correlated with age of mice. Anti-CAR antibody inhibited CB3 infection of liver cells in vitro, suggesting that the receptor plays an important role for mediating CB infection of hepatocytes. In summary, these findings provide further insight into the mechanism of CB3 to infect liver.