title: Epstein-Barr virus infection in chronically inflamed periapical granulomas.
abstract: Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Makino
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeichi
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hatori
authors.affiliation: Department of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Bunnai
authors.initials: B
authors.lastname: Ogiso
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis* / Q000821:virology; D005260:Female; D005881:Gingiva / Q000378:metabolism / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010484:Periapical Granuloma / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012333:RNA, Messenger; D014763:Viral Matrix Proteins