The Study Of The Relationship Between Glioma And Human Herpesvirus 6

Glioma is the most common primary brain tumor in adults and is highly fatal. However, the etiology of glioma was unclear until now. Recent studies have suggested that viral agents might be the etiological factors for glioma.Human herpesvirus-6(HHV-6) was first isolated from lymphoid hyperplasia and peripheral blood mononuclear cells of AIDS patients by Salahuddin in the American Cancer Center in 1986.It belongs to the herpes virusβsubfamily with human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV).It can be divided into HHV-6 A and B subtype based on gene structure and antigen, which representative strains are GS, U1102 and Z29 strains.Some studies have demonstrated that HHV-6 was associated with glioma.A number of articles have reported that they have detected HHV-6 DNA in glioma tissue, but they failed to get the virus. We got a strain of HHV-6 which was isolated from glioma cyst fluid. It was the first report that virus was isolated from glioma. Therefore, we further explored the HHV-6 infection in the development of glioma based on above results.This paper was divided into two parts.In the first part we detected human herpesvirus infection of 40 cases of clinical glioma tissue and 13 normal brain tissues using nested PCR method.The results showed that the positive rate of HHV-6 DNA in glioma was 42.5%, which was higher than normal brain tissue (7.7%). At the same time we detected the expression of herpesvirus antigen in glioma by immunohistochemical, which showed that the positive rate of HHV-6 early antigen and late antigen were both higher than normal brain tissue.(P =0.03;P=0.014). While using HCMV pp65 antibody, HSV-1 antibody it showed no significant difference (P= 0.229; P = 0.35) between glioma and normal brain tissue. HHV-7 pp85 antigen didn't found neither in glioma nor in normal brain tissue. We used the same method to detected meningioma nucleic acid and protein of herpes virus, but it showed no significant differences compared with normal brain tissue.The results showed that HHV-6 infection was relevant to glioma.First of all, we separated tumor invasive lymphocytes(TIL) from HHV-6 positive and negative glioma according to the nested PCR detection in glioma.Then we used magnetic beads of invasive lymphocytes to separate CD4+T cell to test 3H stimulating with HHV-6 antigen and contrast antigen.According to the result we observed the changes of cell proliferation. It showed significant difference between the response ability of CD4+T cell of TIL separated from HHV-6 positive glioma and HHV-6 negative glioma by viral antigen stimulation (P = 0.001). But it showed no significant difference between the response ability of CD4+T cell of TIL separated from HHV-6 positive glioma and HHV-6 negative glioma by contrast antigen stimulation (P = 0.183). It showed that the response ability of CD4+T cell of TIL separated from HHV-6 positive glioma was lower than HHV-6 negative glioma. The ability of proliferation in CD4+T cell of TIL separated from HHV-6 positive glioma decreased,it was probably one of the immune mechanism of glioma.All experimental results showed that HHV-6 infection was related to the development of glioma. We found CD4+T cell of TIL in HHV-6 positive glioma was lower , it was probably one of the pathogenesis of glioma. CD4+T cell did not only had anti-tumor function, importantly, it also assisted the activation of CD8+ T cell to establish and maintain the memory immune. Our study will provide a new idea of glioma clinical treatment through using antivirus durg.