PMID- 30459721 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 9 DP - 2018 TI - Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas. PG - 2450 LID - 10.3389/fmicb.2018.02450 [doi] LID - 2450 AB - Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors. Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device. Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers. Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism. FAU - Hopken, Merle AU - Hopken M AD - Klinik fur Hals-, Nasen- und Ohrenheilkunde, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. AD - Institut fur Pathologie, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. FAU - Forster, Isabel AU - Forster I AD - Institut fur Pathologie, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. FAU - Maune, Steffen AU - Maune S AD - Klinik fur Hals-, Nasen- und Ohrenheilkunde, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. FAU - Brockmann, Michael AU - Brockmann M AD - Institut fur Pathologie, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. FAU - Schildgen, Oliver AU - Schildgen O AD - Institut fur Pathologie, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. FAU - Schildgen, Verena AU - Schildgen V AD - Institut fur Pathologie, Kliniken der Stadt Koln, Klinikum der Privaten Universitat Witten/Herdecke mit Sitz in Koln, Cologne, Germany. LA - eng PT - Journal Article DEP - 20181016 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC6232770 OTO - NOTNLM OT - human bocavirus OT - oncogenesis OT - persistence OT - primary cell culture OT - tonsil squamous cell carcinoma EDAT- 2018/11/22 06:00 MHDA- 2018/11/22 06:01 PMCR- 2018/10/16 CRDT- 2018/11/22 06:00 PHST- 2018/06/28 00:00 [received] PHST- 2018/09/25 00:00 [accepted] PHST- 2018/11/22 06:00 [entrez] PHST- 2018/11/22 06:00 [pubmed] PHST- 2018/11/22 06:01 [medline] PHST- 2018/10/16 00:00 [pmc-release] AID - 10.3389/fmicb.2018.02450 [doi] PST - epublish SO - Front Microbiol. 2018 Oct 16;9:2450. doi: 10.3389/fmicb.2018.02450. eCollection 2018.