| Title: |
Hepatitis B Virus Blocks the CRE/CREB Complex and Prevents TLR9 Transcription and Function in Human B Cells |
| Authors: |
Tout, Issam; Gomes, Melissa; Ainouze, Michelle; Marotel, Marie; Pecoul, Timothee; Durantel, David; Vaccarella, Salvatore; Dubois, Bertrand; Loustaud-Ratti, Veronique; Walzer, Thierry; Alain, Sophie; Chemin, Isabelle; Hasan, Uzma |
| Source: |
The Journal of Immunology ; volume 201, issue 8, page 2331-2344 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2018 |
| Description: |
Effective B cell responses such as cytokine secretion, proliferation, and Ab-specific responses are essential to clear hepatitis B virus (HBV) infection. However, HBV alters numerous immune pathways to persist in the host. B cell activity depends on activation of the innate sensor TLR9 by viral or bacterial DNA motifs. How HBV can deregulate B cell functions remains unknown. In this study, we show that HBV can enter and decrease TLR9 expression in human primary B cells. Using PBMCs from human blood donors, we show that TLR9 expression was reduced in all peripheral B cells subsets exposed to HBV. B cell function mediated by TLR9, but not TLR7, such as proliferation and proinflammatory cytokines secretion, were abrogated in the presence of HBV; however, global Ig secretion was not downregulated. Mechanistically, we show, using human myeloma B cell line RPMI 8226, that the surface Ag hepatitis B surface Ag was responsible for TLR9 dysfunction. hepatitis B surface Ag suppressed the phosphorylation and thus the activation of the transcription factor CREB, preventing TLR9 promoter activity. Finally, we corroborated our in vitro findings in a cohort of chronic HBV carriers and found that TLR9 expression and function were significantly suppressed. The effect of HBV on TLR9 activity in B cells gives insights into oncoviral immune escape strategies, providing knowledge to develop novel immunotherapeutic approaches in chronic HBV–carrier patients. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.1701726 |
| Availability: |
https://doi.org/10.4049/jimmunol.1701726; https://academic.oup.com/jimmunol/article-pdf/201/8/2331/61431902/ji1701726.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.3FD65469 |
| Database: |
BASE |