Scaglioni P P, Melegari M, Wands J R
Cutaneous Biology Research Center, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown 02129.
Virology. 1994 Nov 15;205(1):112-20. doi: 10.1006/viro.1994.1625.
We have generated and functionally characterized dominant negative core protein variants of the hepadnaviruses to determine their effects on "wild type" viral replication. Plasmids expressing these constructs were introduced into hepatoma cell lines by transient transfection and effects on wild type woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) replication were evaluated by Southern blot analysis of purified viral core particles. WHV and HBV constructs expressing a truncated core protein fused in frame with the C-terminus of the small surface protein were found to inhibit viral replication by 90-95% due to disruption of the viral nucleocapsid assembly process and preventing encapsidation of pregenomic RNA. The antiviral effects were found to be specific for the targeted virus. These results demonstrate that mutants of hepadnaviral core protein may represent a novel class of antiviral agents.
我们已构建了嗜肝DNA病毒的显性负性核心蛋白变体并对其功能进行了表征，以确定它们对“野生型”病毒复制的影响。通过瞬时转染将表达这些构建体的质粒导入肝癌细胞系，并通过对纯化的病毒核心颗粒进行Southern印迹分析，评估其对野生型土拨鼠肝炎病毒（WHV）和乙型肝炎病毒（HBV）复制的影响。发现表达与小表面蛋白C末端框内融合的截短核心蛋白的WHV和HBV构建体可抑制病毒复制90-95%，这是由于病毒核衣壳组装过程受到破坏并阻止了前基因组RNA的包装。发现抗病毒作用对靶向病毒具有特异性。这些结果表明，嗜肝DNA病毒核心蛋白的突变体可能代表一类新型抗病毒剂。
