مورد إلكتروني
Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure
| العنوان: | Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure |
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| بيانات النشر: | National Academy of Sciences 2022-08 |
| تفاصيل مُضافة: | Wang, Bo Tian, Debin Sooryanarain, Harini Mahsoub, Hassan M. Heffron, C. Lynn Hassebroek, Anna M. Meng, Xiang-Jin |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Hepatitis E virus (HEV) infection in pregnant women has a high incidence of developing fulminant hepatic failure (FHF) with significant mortality. Multiple amino acid changes in genotype 1 HEV (HEV-1) are reportedly linked to FHF clinical cases, but experimental confirmation of the roles of these changes in FHF is lacking. By utilizing the HEV-1 indicator replicon and infectious clone, we generated 11 HEV-1 single mutants, each with an individual mutation, and investigated the effect of these mutations on HEV replication and infection in human liver cells. We demonstrated that most of the mutations actually impaired HEV-1 replication efficiency compared with the wild type (WT), likely due to altered physicochemical properties and structural conformations. However, two mutations, A317T and V1120I, significantly increased HEV-1 replication. Notably, these two mutations simultaneously occurred in 100% of 21 HEV-1 variants from patients with FHF in Bangladesh. We further created an HEV-1 A317T/V1120I double mutant and found that it greatly enhanced HEV replication, which may explain the rapid viral replication and severe disease. Furthermore, we tested the effect of these FHF-associated mutations on genotype 3 HEV (HEV-3) replication and found that all the mutants had a reduced level of replication ability and infectivity, which is not unexpected due to distinct infection patterns between HEV-1 and HEV-3. Additionally, we demonstrated that these FHF-associated mutations do not appear to alter their sensitivity to ribavirin (RBV), suggesting that ribavirin remains a viable option for antiviral therapy for patients with FHF. The results have important implications for understanding the mechanism of HEV-1-associated FHF. |
| مصطلحات الفهرس: | hepatitis E Virus (HEV), genotype 1 HEV (HEV-1), fulminant hepatic failure (FHF), FHF-associated HEV-1 mutations, genotype 3 HEV (HEV-3), Article - Refereed |
| DOI: | 10.1073.pnas.2207503119 |
| URL: | |
| الإتاحة: | Open access content. Open access content Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0 |
| ملاحظة: | English |
| أرقام أخرى: | VPI oai:vtechworks.lib.vt.edu:10919/115086 doi:10.1073/pnas.2207503119 EISSN:1091-6490 1389730677 |
| المصدر المساهم: | VIRGINIA TECH From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1389730677 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1073.pnas.2207503119 |
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