551
552K. YAMANISHI balloon-like cells could be observed. When the cells were fixed and stained with the sera of acute and convalescent phase of ES, positive staining was observed only with the convalescent sera. Next, the cultured cells were observed by electron microscopy (EM) as reported elsewhere (74). The typical herpesvirus particles were found in the nucleus and cytoplasm of the cultured cells. Thus, the diameter of virion was 90-110 nm in the nucleus and 150-170 nm in the cytoplasm (91, 95), suggesting that this virus resembles a herpesvirus. Next, sera, which were specific for 5 human pathogenic herpesviruses described above, were tested for the reactivity to this viral antigen in the cultured cells, and no positive staining was observed. These results suggested that a new herpesvirus was isolated from ES patients. Then this viral antigen and HHV-6 antigen (55) were reacted with paired sera from ES patients. No antibody to both antigens was detected in the sera during the acute phase and the antibody titers to both antigens increased during the convalescent phase. This result indicated that the virus isolated from ES patients was HHV-6. Thereafter this result was confirmed by other groups, and the virus isolation rate from ES patients was shown to be high at the febrile phase of ES (6, 13). Furthermore, it was reported that HHV-6 infection without clinical symptoms of rash or fever, or even without any clinical symptoms could be seen in some individuals as the primary infection of 81,83).3. Other diseases associated with HHV-6 infection. Although the symptoms of ES are relatively mild, liver dysfunction and neurological symptoms such as convulsion are seen during ES (62). Recently it has been reported that HHV-6 caused the liver dysfunction in the patients who were in the primary infection of HHV-6 (9, 82, 88), and that unfortunately one patient died from fulminant hepatitis (9).A case that was diagnosed as encephalitis during HHV-6 infection was also reported (36). In order to detect HHV-6 in the central nervous system, we tried to detect HHV-6 DNA in the cerebrospinal fluid (CSF) from ES patients (93). CSF was obtained from patients showing the neurological symptoms, such as convulsion, vomiting, irritability and bulging of anterior fontanel, during febrile phase of ES. Since patients had high fever (more than 39 C) and the appearance of rash after subsidence of the fever, they were clinically diagnosed as ES. When cell counts in CSF were performed at the time of sample collection, they ranged in normal in each sample. CSF samples as controls were collected from patients who were admitted in the hospital and suspected as having neurological symptoms or lasting high fever by unknown causes. Sixteen specimens including 6 control samples of CSF were collected from the patients, and DNA was extracted and amplified by PCR using HHV-6 specific primers. The band specific for HHV-6 DNA could be detected by ethidium bromide staining in 5 of the 10 ES patients, CSF (50%), and this was confirmed by Southern blot...