دورية أكاديمية
The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro
| العنوان: | The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro |
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| المؤلفون: | Salpini R., Surdo M., Cortese M. F., Palumbo G. A., Carioti L., Cappiello G., Spano A., Trimoulet P., Fleury H., Vecchiet J., Pasquazzi C., Mirabelli C., Scutari R., Sacco A., Alkhatib M., Missale G., Francioso S., Sarmati L., Andreoni M., Angelico M., Ceccherini-Silberstein F., Levrero M., Perno C. F., Belloni L., Svicher V. |
| المساهمون: | Salpini, R., Surdo, M., Cortese, M. F., Palumbo, G. A., Carioti, L., Cappiello, G., Spano, A., Trimoulet, P., Fleury, H., Vecchiet, J., Pasquazzi, C., Mirabelli, C., Scutari, R., Sacco, A., Alkhatib, M., Missale, G., Francioso, S., Sarmati, L., Andreoni, M., Angelico, M., Ceccherini-Silberstein, F., Levrero, M., Perno, C. F., Belloni, L., Svicher, V. |
| سنة النشر: | 2019 |
| المجموعة: | ARUd'A - Archivio Istituzionale della ricerca dell'università Chieti-Pescara (IRIS) |
| مصطلحات موضوعية: | Apoptosi, HBx, Hepatitis B, Hepatitis B virus replication, Hepatocellular carcinoma |
| الوصف: | OBJECTIVE: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. METHODS: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pre-genomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. RESULTS: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/30472417; info:eu-repo/semantics/altIdentifier/wos/WOS:000470850400025; volume:25; issue:7; firstpage:906.e1; lastpage:906.e7; numberofpages:7; journal:CLINICAL MICROBIOLOGY AND INFECTION; https://hdl.handle.net/11564/705359Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85058217511; http://onlinelibrary.wiley.com/journal/10.1111Test/(ISSN)1469-0691 |
| DOI: | 10.1016/j.cmi.2018.11.017 |
| DOI: | 10.1111/(ISSN)1469-0691 |
| الإتاحة: | https://doi.org/10.1016/j.cmi.2018.11.017Test https://hdl.handle.net/11564/705359Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7772566D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.cmi.2018.11.017 |
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