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However, before HBV infection can be adequately controlled, many mysteries about the HBV life cycle must be solved. In this study, TIMM29, an inner mitochondrial membrane protein, was identified as an interaction partner of the preS1 region of the HBV large S protein. The interaction was verified by both an immunoprecipitation with preS1 peptides and a GST\u2010pulldown assay. Immunofluorescence studies also showed colocalization of preS1 and TIMM29. Moreover, it was determined that the preS1 bound with amino acids 92\u2013189 of the TIMM29 protein. Infection of HBV in TIMM29\u2010overexpressing NTCP\/G2 cells resulted in a significant decrease of HBeAg and both extracellular particle\u2010associated and core particle\u2010associated HBV DNA without affecting cccDNA formation. Comparable results were obtained with TIMM29\u2010overexpressing HB611 cells, which constitutively produce HBV. In contrast, knockout of TIMM29 in NTCP\/G2 cells led to a higher production of HBV including HBeAg expression, as did knockout of TIMM29 in HB611. Collectively, these results suggested that TIMM29 interacts with the preS1 region of the HBV large S protein and modulates HBV amplification.<\/jats:p>","DOI":"10.1111\/1348-0421.12852","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T18:35:13Z","timestamp":1600972513000},"page":"792-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["TIMM29 interacts with hepatitis B virus preS1 to modulate the HBV life cycle"],"prefix":"10.1111","volume":"64","author":[{"given":"Nelly Gakii","family":"Muriungi","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Microbiology and Immunology Osaka University Graduate School of Medicine 2\u20102 Yamada\u2010oka Suita Osaka 565\u20100871 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-8105","authenticated-orcid":false,"given":"Keiji","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Microbiology and Immunology Osaka University Graduate School of Medicine 2\u20102 Yamada\u2010oka Suita Osaka 565\u20100871 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.1.51-68.2000"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(05)00384-7"},{"key":"e_1_2_10_4_1","unstructured":"WHO. 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