X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo.
X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo.
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DOI：
10.1172/jci13787
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发表时间：
2001-11
期刊：
影响因子：
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通讯作者：
Zhensheng Zhang;N. Torii;Zongyi Hu;J. Jacob;T. Liang
中科院分区：
文献类型：
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作者：
Zhensheng Zhang;N. Torii;Zongyi Hu;J. Jacob;T. Liang
乙型肝炎病毒 (HBV) 的 X 蛋白 (HBX) 已被证明对于体内 HBV 感染的建立非常重要。我们之前的研究表明，HBX 与蛋白酶体复合物的相互作用可能是 HBX 多效性功能的基础。在这项研究中，我们产生了一系列土拨鼠肝炎病毒（WHV）X突变体，包括与蛋白酶体相互作用的结构域的突变体，并研究了它们在土拨鼠中的感染性。许多突变体存在反式激活缺陷，但没有一个突变体在体外存在完全复制缺陷。在体内，所有野生型和一些 X 突变体转染的动物都表现出感染抗 WHc 和/或抗 WHs 血清转化的证据。大多数野生型和X突变体转染的动物有短暂的病毒血症。一些动物后来受到传染性 WHV 的攻击。接种 X 突变体的动物，包括那些没有感染血清学证据的动物，受到保护免受攻击，这表明以前的感染产生了保护性免疫力。我们的研究表明，先前描述的 HBX 功能域具有重要的生物学意义，并且 X 缺陷突变体（可能作为减毒病毒）在体内并不完全存在复制缺陷。
The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant-transfected animals demonstrated evidence of infection with anti-WHc and/or anti-WHs seroconversion. Most of the wild-type- and X mutant-transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo.