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Recently, the family Polyomaviridae was classified as 3 genera, such as Orthopolyomavirus, Wukipolyomavirus which contain mammalian polyomaviruses and Avipolyomavirus which only contain avian polyomaviruses. We have recently isolated novel polyomaviruses, including Mastomys Polyoamvirus (MasPyV) and Vervet monkey Polyoamvirus-1 (VmPyV-1) by epidemiological activities and examined functions of their encoding proteins. In addition, we have been investigating the mechanisms of replication of human polyomavirus, JC polyomavirus (JCPyV). We recently obtained the results of function of JCVPyV-encoding proteins, including early protein (Large T antigen) and late proteins (VP1 and Agno). In this review, we summarized the data of our basic research activities.

The objective of this study was to determine the prevalence of human papillomavirus(HPV) infection in vaginal papillomatous lesions diagnosed in Tsuji Ladies Clinic. From January, 2000 to February, 2001, 52 patients were diagnosed with condyloma acuminata in the Clinic. All the patients received a complete gynecologic examination including colposcopic evaluation, and HPV DNA was assayed for in cervicovaginal lavages using polymerase chain reaction. HPV was detected in 31 of the 52 (60%) patients, and high risk HPV was found in 23 patients(45%). The incidence of high risk HPV infection is very high in vaginal condyloma acuminata. Detection of high risk HPV-positive women suggests that they may also be at risk for developing carcinoma. Therefore, it is very important to follow-up patients with condyloma acuminata.

We studied retrospectively 212 patients with parotid tumors who were treated in our hospital between October 1981 and March 1998. One hundred seventy-two of the tumors were benign, and 40 of them were malignant. The tumors were bilateral in 13 patients. Since 1992, we have treated at least 1 bilateral parotid tumor patient per year, and the number of patients with bilateral parotid tumors has tended to increase. Histologically, adenolymphomas occurred in 11 patients, and there was one occurrence of pleomorphic adenoma and one occurrence of basal cell adenoma. Eighty-five percent of all bilateral parotid tumors were adenolymphomas, and the bilateral parotid tumors comprised twenty percent (11 of 53 patients) of all adenolymphomas that we encountered. Among the 13 patients with bilateral parotid tumors, 1 patient experienced them heterochronously. In 7 of the 13 patients the tumor on the opposite side was found by diagnostic imaging. One patient showed recurrence in both parotid glands 4 years after initial surgery. Comparing bilareral adenolymphomas with unilateral adenolymphomas, there was no significant difference in the age or sex of the patients. Regarding bilateral adenolymphoma, 4 patients showed a solitary tumor on either side, 4 patients showed a solitary tumor on one side and multiple tumors on the other side, and 4 patients showed multiple bilateral tumors. Regarding unilateral adenolymphoma, 38 patients showed solitary tumors and 4 patients showed multiple tumors. Bilateral adenolymphomas were more multicentric than unilateral adenolymphomas. Epstein-Barr virus-encoded RNA (EBER) was detected in 11 of the 12 bilateral adenolymphomas and in 18 of 35 patients with unilateral adenolymphoma, by in situ hybridization. EBER was detected more frequently in the multiple unilateral adenolymphomas than in the solitary unilateral adenolymphomas. Based on our experience, the bilateral parotid tumor is not rare. Care should be taken to observe the other side of the parotid gland with parotid tumors that are suspected adenolymphomas. Imaging may be helpful for the detection of bilateral tumors. A relationship may exist between Epstein-Barr virus and adenolymphoma multicentricity.

We analysed the characteristics of 372 Epstein-Barr virus (EBV) infected patients visiting our hospital from 1981 to 1995 classifying the phase I (from 1981 to 1988), the phase II (from 1989 to 1991) and the phase III (from 1992 to 1995). The incidence of infectious mononucleosis (IM) as EBV primary infection increased especially in the patients over 30 years old in the phase II and III. Immunological data on EBV specific antibodies showed twice positivity for anti EBV VCA-Igm antibody and the patients with anti-EBNA antibody decreased in the phase II and III. It is indicative of early diagnosis on primary EBV infection. EBV also causes atypical diseases, non-IM in this report, including hematological or neurological disorders. In hematological ones, one of 4 cases with virus associated hemophagocytic syndrome (VAHS) took fatal courses in the phase I, others had recovered by early diagnosis and adequate therapies (pulse therapy of steroids, exchange transfusion etc.). We indicated here the increased number and advanced age of patients with IM and improvement of the early diagnosis in recent 6 years compared with the previous 8 years.

Contagion with certain types of HPV was supposed to have a causal relationship with cervical neoplasia of the uterus. The rate of prevalence of HPV was investigated in pre-cancer and cancer patients with uterine cervical smear using virapap or viratype. According to the cytologic classification, among those whose cytology was diagnosed as class I or II, were found a few positive HPV, however, in cases in classes cytology IIIa, III and IIIb, the positive rate turned out to be 22.5, 41 and 72.4%, respectively. About 65% of patients whose post-operative diagnosis was cervical carcinoma, had been found positive in the pre-operative HPV.DNA check up. The statistical profiles of virally infected subjects were regarded as slightly younger females with early onset of menarche. A higher positive rate was found in such groups such as unmarried single and divorced single women, career employees with special skills, housewives and dwellers in residential and commercial sections. The follow up study of HPV infection was checked with subjects with dysplasia, and no case was recognized in which initially HPV negative dysplasia turned to positive during the observation period. But, in about 50% of those checked, initially HPV positive dysplasia turned to negative, during the follow up period. In the cases with long term (more than 8 years) dysplasia which was followed up, only one out of 10 was found to be HPV positive, while in middle term (more than 2 years but less than 8 years) followed up dysplasia, the positive rate was calculated as 47.8%.

JC virus (JCV) and BK virus (BKV) are known as small DNA type tumor viruses belonging to the human polyoma virus. The infectious state of these viruses has not yet been examined extensively in the aged persons; therefore, antibody measurements were made in 349 healthy volunteers from 20 to 90 years old and 383 cases of in-patients from 60 to 100 years old. As controls, measurements were made on the antibody titers to the herpes-type viruses which are known to be reactivated as the immunologic state of hosts decrease. The results obtained were as follows; 1) In the aged cases over 60 years old, the average HI antibody titers for JCV were significantly higher than that for BKV. 2) In the aged persons of the prevalence rate the high antibody titer (1024 less than) for JCV was also higher than that for BKV. 3) In the results with EIA (EIA test human polyoma viruses common antigen), the significant increase in the antibody titer was observed in the aged older than 70. 4) The average antibody titers of HSV and CMV, tended to increase as the age advanced until 60 and to decrease with age over 70. These results indicate that JCV is reactivated in a high rate in the aged (70 less than) persons.

A nation-wide sero-epidemiologic survey of adult T-cell leukemia virus (ATLV) detected as anti-ATLA (ATLV-associated antigen) was made in Japan. Sera from adult donors in 15 different locations were screened for anti-ATLA. High incidences (6 to 37%) of antibody-positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV-endemic areas corresponding to ATL-endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL-endemic areas showed an age-dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti-ATLA was found in all but two of 142 patients with ATL. Anti-ATLA-positive patients with ATL were mainly found in ATLV-endemic areas, and only a few in ATL-nonendemic areas. Six patients with cutaneous T-cell lymphoma in ATLV-nonendemic areas gave a negative reaction for anti-ATLA. The geometric mean titer of anti-ATLA of patients with ATL was higher than that of healthy donors.