PMID- 37243264 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20230530 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 15 IP - 5 DP - 2023 May 16 TI - Super-Resolution Microscopy Analysis of Hepatitis B Viral cccDNA and Host Factors. LID - 10.3390/v15051178 [doi] LID - 1178 AB - Infection with hepatitis B virus (HBV) cannot be cured completely because of the persistence of covalently closed circular DNA (cccDNA). We previously found that the host gene dedicator of cytokinesis 11 (DOCK11) was required for HBV persistence. In this study, we further investigated the mechanism that links DOCK11 to other host genes in the regulation of cccDNA transcription. cccDNA levels were determined by quantitative real-time polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) in stable HBV-producing cell lines and HBV-infected PXB-cells(R). Interactions between DOCK11 and other host genes were identified by super-resolution microscopy, immunoblotting, and chromatin immunoprecipitation. FISH facilitated the subcellular localization of key HBV nucleic acids. Interestingly, although DOCK11 partially colocalized with histone proteins, such as H3K4me3 and H3K27me3, and nonhistone proteins, such as RNA Pol II, it played limited roles in histone modification and RNA transcription. DOCK11 was functionally involved in regulating the subnuclear distribution of host factors and/or cccDNA, resulting in an increase in cccDNA closely located to H3K4me3 and RNA Pol II for activating cccDNA transcription. Thus, it was suggested that the association of cccDNA-bound Pol II and H3K4me3 required the assistance of DOCK11. DOCK11 facilitated the association of cccDNA with H3K4me3 and RNA Pol II. FAU - Doan, Phuong Thi Bich AU - Doan PTB AUID- ORCID: 0000-0002-0363-5250 AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Nio, Kouki AU - Nio K AUID- ORCID: 0000-0002-0971-8313 AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Shimakami, Tetsuro AU - Shimakami T AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Kuroki, Kazuyuki AU - Kuroki K AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Li, Ying-Yi AU - Li YY AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Sugimoto, Saiho AU - Sugimoto S AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Takayama, Hideo AU - Takayama H AUID- ORCID: 0000-0001-8247-483X AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Okada, Hikari AU - Okada H AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Kaneko, Shuichi AU - Kaneko S AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Honda, Masao AU - Honda M AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. FAU - Yamashita, Taro AU - Yamashita T AUID- ORCID: 0000-0002-3383-9131 AD - Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230516 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - EC 2.7.7.- (RNA Polymerase II) RN - 0 (DNA, Viral) RN - 0 (DNA, Circular) SB - IM MH - Humans MH - RNA Polymerase II/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Microscopy MH - Virus Replication/genetics MH - DNA, Viral/genetics/metabolism MH - Hepatitis B virus/physiology MH - DNA, Circular/genetics/metabolism MH - *Hepatitis B/genetics MH - *Hepatitis B, Chronic PMC - PMC10223333 OTO - NOTNLM OT - H3K4me3 OT - HBV OT - RNA Pol II OT - fluorescence in in situ hybridization FISH OT - transcription factors COIS- The authors declare no conflict of interest. EDAT- 2023/05/27 09:43 MHDA- 2023/05/29 06:42 PMCR- 2023/05/16 CRDT- 2023/05/27 01:33 PHST- 2023/04/18 00:00 [received] PHST- 2023/05/13 00:00 [revised] PHST- 2023/05/15 00:00 [accepted] PHST- 2023/05/29 06:42 [medline] PHST- 2023/05/27 09:43 [pubmed] PHST- 2023/05/27 01:33 [entrez] PHST- 2023/05/16 00:00 [pmc-release] AID - v15051178 [pii] AID - viruses-15-01178 [pii] AID - 10.3390/v15051178 [doi] PST - epublish SO - Viruses. 2023 May 16;15(5):1178. doi: 10.3390/v15051178.