Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution Nagoya University
2.Research Area Life Sciences
3.Research Field Infectious Diseases and Bioregulation
4.Term of Project FY 1997 〜 FY 2001
5.Project Number 97L00703
6.Title of Project Studies on Molecular Basis of Herpesvirus Infections

7.Project Leader
Name Institution,Department Title of Position
Yukihiro Nishiyama Nagoya University , Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Yasunobu Yoshikai Nagoya University, Graduate School of Medicine Professor
Tuneo Morishima Nagoya University, Faculty of Medicine Professor
Tatsuya Tsurumi Aichi Cancer Center, Research Institute, Laboratory of Viral Oncology Chief

9.Summary of Research Results

I ) Studies on the function of herpesvirus gene products. Herpesviruses are large DNA viruses whose genomes consist of a linear ds DNA molecule, 125-229 kbp. Among them, herpes simplex virus (HSV), a neurotropic human pathogen, has been most extensively studied as the prototype. Although HSV has been shown to encode at least 74 genes, the function and roles of many genes are still unkonwn. We have identified and characterized more than 20 gene products of HSV with unkown functions, and found that some of them have very interesting, unique properties; 1) US3 encodes a serine/threonine kinase which protects infected cells from apoptotic cell death; 2) UL14 protein, which can translocate the minor capsid protein and DNA cleavage/packaging proteins into the nucleus, has heat shock protein-like functions; 3) UL21 protein colocalizes and physically associates with microtubules, and promotes the long cellular processes in overexpressing cells; 4) US11 protein has intercellular trafficking activity and accumulates in the nucleolus in singly expressing cells; 5) UL56 protein is a tail-anchored type II membrane protein which localizes to both the Golgi apparatus and cyoplasmic vesicles.
II ) Studies on the immune response against HSV infection. Our studies have demonstrated the importance of memory type CD8+T cells and IL-15 in the protection against systemic HSV type 2 infection. We also investigated the effects of US2 and US3 deficiencies of HSV-2 on host immunity in a murine model of genital herpes infection, and found that a US3 deficiency dramatically alters the induction of the host immune response.
III ) Clinical studies on herpesvirus infections. We have established a rapid system to quantify herpesvirus DNAs using a real-time PCR method, and found that measuring viral loads is very useful for predicting the progression and evaluating the efficacy of treatment in a variety of human herpesvirus infections. We also found correlation between HHV-6 infection and skin rash after allogeneic BMT and that posttransplantation HHV-6 viremia occured more frequently in recipients with leukemia or lympoma than in recipients with other diseases.

10.Key Words

(1)Herpesviruses、(2)Herpes simplex virus、(3)Viral gene function
(4)Viral DNA replication、(5)Virus-host interaction、(6)Viral pathogenesis
(7)Human herpesvirus infection、(8)Cell-mediated immunity