Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
| العنوان: | Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice |
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| المؤلفون: | Ansgar W. Lohse, Maria Buti, Camille Sureau, Maria Homs, Katja Giersch, Jörg Petersen, Tassilo Volz, Lena Allweiss, Teresa Pollicino, Marc Lütgehetmann, Martina Helbig, Maura Dandri |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Hepatitis B virus, HBsAg, Guanine, Science, viruses, Alpha interferon, Viremia, Biology, medicine.disease_cause, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Interferon, Pegylated interferon, medicine, Animals, Humans, Transplantation Chimera, Multidisciplinary, Coinfection, HDV, HBV, interferon alpha, HBV/HDV infected humanized mice, Interferon-alpha, virus diseases, biochemical phenomena, metabolism, and nutrition, Hepatitis B, medicine.disease, Hepatitis D, Virology, Liver Transplantation, Disease Models, Animal, 030104 developmental biology, Immunology, Heterografts, Medicine, 030211 gastroenterology & hepatology, Hepatitis Delta Virus, Biomarkers, medicine.drug |
| الوصف: | Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28f4dda3736fd4d01c6b30d6ebd1fea0 https://doi.org/10.1038/s41598-017-03946-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....28f4dda3736fd4d01c6b30d6ebd1fea0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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