Studies on the functions of herpesvirus genes involved in evading the host immune system

疱疹病毒是一种大的DNA病毒，其基因组由125-229kbp的线性dsDNA分子组成，包含大约80-200个基因。最近的研究表明，大型DNA病毒具有许多干扰宿主免疫系统特定部分的基因，如干扰素、补体、细胞因子、中和抗体和细胞毒性T淋巴细胞识别。在本研究中，我们进一步研究了疱疹病毒US3基因的功能，并试图发现参与免疫逃避的新的病毒基因。1)我们已经报道，单纯疱疹病毒US3基因的表达对病毒在巨噬细胞中的生长是必不可少的。我们成功地获得了针对US3产物的特异性抗体，研究表明US3产物定位于感染中期的细胞核中。2)HSV糖蛋白C(GC)被证明具有结合补体C3b片段的活性。3)构建了功能未知的HSV基因表达载体，并获得了针对UL3、UL4、UL16、UL51、US2和US10.4基因产物的特异性抗体。4)我们已报道人巨细胞病毒(HCMV)感染可降低细胞表面MHC-I类分子的表达。然而，目前的研究表明，不完整的CMV颗粒在MHC-I类表达上调中起着重要作用。

Herpesviruses are large DNA viruses whose genomes consist of a linear dsDNA molecule, 125-229kbp, and contain from approximately 80 to 200genes. Recent studies have shown that large DNA viruses possess many genes which interfere with specific parts of the host immune system such as interferons, complements, cytokines, neutralizing antibodies and cytotoxic T lymphocyte recognition. In this study, we have further studied the function of such genes of herpesviruses and also tried to identify new viral genes involved in the immune evasion.1) We have reported that the expression of US3 gene of herpes simplex virus (HSV) is essential for the viral growth in macrophages. We succeeded to get specific antibodies to the US3 product, and sutdies revealed that the US3 product is localized in the nucleus at the middle stage of infection.2) Glycoprotein C (gC) of HSV has been shown to have an activity to bind the C3b fragment of complement. We found that gC is not imortant in spreading to the central nervous system but in/to the epithelial cells of broncioles in the mouse.3) We constructed the expression vectors of HSV genes whose functions have been unknown, and could obtain specific antibodies against the products of UL3, UL4, UL16, UL51, US2 and US10.4) We have reported that human cytomegalovirus (HCMV) infection reduces MHC class I expression on the cell surface. The present study, however, suggest that incomplete CMV particles play an important role in the up-regulation of MHC class I expression.