Impacts of HBV rtH55R Polymerase Substitution on Viral Replication and rtM204I/V Resistance to Nucleoside/Nucleotide Antiviral Drugs

Xiang, Kuanhui; Zhao, Chengyu; Wang, Shuai; Li, Yao; Su, Mingze; Wang, Qiangyi; Xu, Xizhan; Deng, Juan; Zhang, Hui; Li, Tong

doi:10.3851/imp3170

Cited by 5 publications

(1 citation statement)

References 28 publications

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“…Hepatitis B virus sequences X and RT regions were amplified from tissues samples and sequenced as described previously ( Xiang et al, 2018 ). HBV S gene was obtained from RT due to its overlap with RT region.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

Xiao

Cao²,

Zhang³

et al. 2022

Front. Microbiol.

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BackgroundThe existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients.MethodsWe collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis.ResultsWe found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44.ConclusionHBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.

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Section: Methodsmentioning

confidence: 99%

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

Xiao

Cao²,

Zhang³

et al. 2022

Front. Microbiol.

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The modulation of HBsAg level by sI126T is affected by additional amino acid substitutions in the S region of HBV

et al. 2019

Infection, Genetics and Evolution

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Characterization of mutations in the reverse transcriptase region of hepatitis B virus in treated and untreated chronic hepatitis B patients

Zou

Qian

Fang

et al. 2020

Transactions of the Royal Society of Tropical Medicine and Hygiene

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Background The reverse transcriptase (RT) region of the hepatitis B virus (HBV) is the target of antiviral treatment. However, the discrepancy in RT mutations between nucleos(t)ide analogue (NA)-treated and -untreated chronic hepatitis B (CHB) patients is un clear. Methods Serum samples were collected from 119 NA-treated and 135 NA-untreated patients. The sampling time was decided by the clinician. Full-length HBV RT regions were amplified using nest polymerase chain reaction. The mutations within the RT region were analysed by direct sequencing. Results The incidence of RT mutations in treated patients was higher than that in untreated patients (p<0.05). The classic drug-resistant mutations were detected in 44.5% (53/119) of treated patients, which was significantly higher than in untreated patients (6.7% [9/135]) (p<0.05). The non-classical mutations showed their complexity and diversity in both patient groups. Multiple mutations (three or more) were more frequent in treated patients than in untreated patients (p<0.05). Several novel mutations might be related to NA resistance. Conclusions The selection pressures of NAs accelerated the development of RT mutations, especially within the functional domain. Mutations in the RT region occurred not only at classical sites, but also at other non-classical sites, which might be related to drug resistance and/or viral replication. The biological function and fitness of HBV isolates harbouring these novel mutations need further in vitro and in vivo verification experiments.

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Impacts of HBV rtH55R Polymerase Substitution on Viral Replication and rtM204I/V Resistance to Nucleoside/Nucleotide Antiviral Drugs

Cited by 5 publications

References 28 publications

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

The modulation of HBsAg level by sI126T is affected by additional amino acid substitutions in the S region of HBV

Characterization of mutations in the reverse transcriptase region of hepatitis B virus in treated and untreated chronic hepatitis B patients

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