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Association Between Adeno-associated Virus 2 and Neurologic Complications of Pediatric Human Herpesvirus-6B Infection
Jun-Ichi Kawada1, Yuki Higashimoto2, Yoshiki Kawamura1,3
1From the Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Background:
Recent studies have reported the possible link between adeno-associated virus 2 (AAV2) and severe pediatric acute hepatitis. It has been suggested that aberrant AAV2 replication initiated by coinfection with "helper viruses" such as human adenovirus and human herpesvirus-6B (HHV-6B) may induce abnormal immune responses. Encephalitis/encephalopathy is a severe complication of primary HHV-6B infection, but the underlying mechanisms remain unclear. This study analyzed the association between AAV2 coinfection and neurologic complications of primary HHV-6B infection in children.
Methods:
Preserved serum samples obtained from 36 patients with HHV-6B-associated encephalitis/encephalopathy, 39 with febrile seizure, and 83 without neurologic complications were retrospectively analyzed. Primary HHV-6B infection was confirmed if HHV-6B DNA was detected and the HHV-6B antibody was negative in serum. AAV2 and HHV-6 DNA loads were quantitated using real-time PCR.
Results:
AAV2 was detected in 4 (11%) and 3 (8%) patients in the encephalitis/encephalopathy and febrile seizure groups, respectively. In contrast, AAV2 was undetectable in 83 patients without neurologic complications. AAV2 detection frequency was significantly higher in the encephalitis/encephalopathy and febrile seizure groups compared with the no neurologic complications group ( P = 0.01 and P = 0.03, respectively). Among 4 patients with HHV-6B-associated encephalitis/encephalopathy, AAV2 DNA was detected in the cerebrospinal fluid of 2 patients. Serum HHV-6B DNA load was not significantly different among patients who were AAV2 positive or AAV negative and with or without neurologic complications.
Conclusions:
These findings suggest that coinfection of AAV2 and HHV-6B is associated with neurologic complications such as encephalitis/encephalopathy and febrile seizure in children.
