Differences in HBV Replication, APOBEC3 Family Expression, and Inflammatory Cytokine Levels Between Wild-Type HBV and Pre-core (G1896A) or Basal Core Promoter (A1762T/G1764A) Mutants
| العنوان: | Differences in HBV Replication, APOBEC3 Family Expression, and Inflammatory Cytokine Levels Between Wild-Type HBV and Pre-core (G1896A) or Basal Core Promoter (A1762T/G1764A) Mutants |
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| المؤلفون: | Keith C. K. Lau, Shivali S. Joshi, Douglas J. Mahoney, Andrew L. Mason, Guido van Marle, Carla Osiowy, Carla S. Coffin |
| المصدر: | Frontiers in Microbiology Frontiers in Microbiology, Vol 11 (2020) |
| بيانات النشر: | Frontiers Media SA, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Microbiology (medical), HBsAg, Chemokine, medicine.medical_treatment, lcsh:QR1-502, viral hepatitis, Biology, Microbiology, lcsh:Microbiology, Virus, 03 medical and health sciences, HBV precore/basal core promoter mutations, APOBEC3 family, medicine, Original Research, 030304 developmental biology, 0303 health sciences, 030306 microbiology, genetic variants, in vitro characterization, Wild type, virus diseases, Promoter, Molecular biology, digestive system diseases, Cytokine, HBeAg, Viral replication, biology.protein |
| الوصف: | Background Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) world-wide. HBV variants, particularly the G1896A pre-core (PC) and A1762T/G1764A basal core promoter (BCP) mutations, are established risk factors for cirrhosis and HCC, but the molecular biological basis is unclear. We hypothesized that these variants result in differential HBV replication, APOBEC3 family expression, and cytokine/chemokine expression. Methods HepG2 cells were transfected with monomeric full-length containing wild-type, PC, or BCP HBV. Cells and supernatant were collected to analyze viral infection markers (i.e., HBsAg, HBeAg, HBV DNA, and RNA). Cellular APOBEC3 expression and activity was assessed by quantitative real-time (qRT)-PCR, immunoblot, differential DNA denaturation PCR, and sequencing. Cytokine/chemokines in the supernatant and in serum from 11 CHB carriers (4 non-cirrhotic; 7 cirrhotic and/or HCC) with predominantly wild-type, PC, or BCP variants were evaluated by Luminex. Results HBeAg expression was reduced in PC and BCP variants, and higher supernatant HBV DNA and HBV RNA levels were found with A1762T/G1764A vs. G1896A mutant (p < 0.05). Increased APOBEC3G protein levels in wild-type vs. mutant were not associated with HBV covalently closed circular DNA G-to-A hypermutations. Differences in cytokine/chemokine expression in culture supernatants, especially IL-13 were observed amongst the variants analyzed. Noticeable increases of numerous cytokines/chemokines, including IL-4 and IL-8, were observed in ex vivo serum collected from CHB carriers with PC mutant. Conclusion HBV sequence variation leads to differences in HBV protein production (HBeAg) and viral replication in addition to altered host innate antiviral restriction factor (APOBEC3) and cytokine/chemokine expression. |
| تدمد: | 1664-302X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::381e20ff148a2f1c67b73412f0459c26Test https://doi.org/10.3389/fmicb.2020.01653Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....381e20ff148a2f1c67b73412f0459c26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1664302X |
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