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

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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.