Hepatitis B virus genetic mutations and evolution in liver diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Shen T
PROVIDER: S-EPMC4017059 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Publications
Hepatitis B virus genetic mutations and evolution in liver diseases.
World journal of gastroenterology 20140501 18
Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the Hepadnaviridae family and is approximately 3.2 kb in length. Owing to a lack of proofreading capacity during reverse transcription and a high replication rate, HBV exhibits as quasispecies. To detect the genetic mutations of HBV, many methods with different sensitivities and throughputs were developed. According to documentary records, HBV mutation and evolution were important vial parameters in predicting disease progression ...[more]
Similar Datasets
Project description:ObjectivesThe study was designed to characterize the surface, core promoter, precore/core region sequences for the presence of mutations in hepatitis B virus (HBV) associated with different liver diseases.Methods567 HBV associated patients with different liver diseases were enrolled in this study. All samples were analyzed for HBV surface, core promoter, precore/core region mutations and genotypes using PCR and direct sequencing.ResultsHBV genotype D (72.8%) was the predominant type followed by genotype A (27.2%). The serum viral load of HBV was highest in HBsAg carriers group and lowest in patients with hepatocellular carcinoma. 17.9% patients with cirrhosis and 24.6% hepatocellular carcinoma cases were ADV-resistant with rtA181T/V mutations in the S-gene. A1896T was found more frequently in fulminant hepatic failure compared to acute viral hepatitis patients (p = 0.038). T1753V mutation was significantly higher in patients with cirrhosis of liver (34.6%) than in chronic hepatitis (18.9%) and hepatocellular carcinoma patients (21.2%; p = 0.001). T1762/A1764 mutation was observed in all the groups. C1914G core gene mutation was associated with the hepatocellular carcinoma (32.2%) compared to other groups. HBV genotype D predominated in comparison to genotype A. An increased frequency of precore mutation and BCP double mutations amongst the population studied was also observed.ConclusionMutations such as T1762/A1764, T1753V and C1914G were usually associated with advanced forms of liver disease and had an increased risk of HCC. The nucleotide variability in the basal core promoter and precore regions possibly plays a role in the progression of HBV disease. Prospective studies on the sequence variations of the preC/C region of the HBV genome and the molecular mechanisms in relation to progression of liver disease would aid in better understanding of the biological significance of HBV strains in India.
| S-EPMC3375258 | biostudies-literature
Project description:Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a single-stranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection.
| S-EPMC4411526 | biostudies-literature
Project description:Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal-oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV.
| S-EPMC6563261 | biostudies-literature
Project description:BackgroundThe geographical distribution of hepatitis B virus (HBV) and hepatitis D virus (HDV) genotypes is uneven and has its own clinical and organizational implications for health systems. Despite the introduction of vaccination and successful antiviral therapy the prevalence of chronic hepatitis B (with or without delta agent) increased over the past 5 years. This study aimed for the first time to investigate the molecular epidemiology of HBV and HDV in Kazakhstan.MethodsTotal 834 chronic hepatitis B (with or without delta agent) patients were included to the study from November 2017 to June 2019. The material was collected from the regional hepatological сenters from 13 cities of Kazakhstan. Genotyping of HBV/HDV isolates was carried out using phylogenetic analysis of null-binary sequences of Kazakhstani isolates, in comparison with the reference sequences. Nucleotide sequence alignment was performed using the ClustalW algorithm, the "neighbor-joining" method was used for the construction of phylogenetic trees and subsequent analysis.ResultsOverall 341 samples were PCR-positive and genotyped for HBV. Comparison and phylogenetic analysis of nucleotide sequences of HBV isolates showed that they were represented by genotypes HBV-D (95.9%), HBV-A (3.5%) and HBV-C (0.6%). At the same time, the identity of the nucleotide sequences of Kazakhstani isolates were: HBV-D (95-100%); HBV-A (97.2-100%) and HBV-C (99%). 256 samples were PCR positive and genotyped for HDV, all of them belonged to genotype 1.ConclusionThis study describes for the first time the molecular epidemiology of HBV and HDV in Kazakhstan. The data obtained expand the knowledge of the global epidemiology of viruses; have potential implications for public health policy and for further clinical research on chronic hepatitis in Kazakhstan.Trial registrationClinicalTrials.gov NCT05095181 (registered on 27/10/2021).
| S-EPMC10426108 | biostudies-literature
Project description:Hepatitis E virus (HEV) infection is a major cause of acute hepatitis but also provokes chronic infection in immunocompromised patients. Although the pathogenesis and treatment outcome involve complex interplay between the virus and host, the nature of adaptive responses of HEV to the host immune system remain obscure at best. In this study, we used large-scale proteomic bioinformatics to profile characteristic mutations in human HEV isolates associated to ribavirin treatment failure, chronic hepatitis, hepatic failure or altered immunoreactivity. The prevalence of specific mutations was examined in a large number of protein sequences of ORF1 and ORF2 regions of the 3 major human-derived HEV genotypes (1, 3 and 4). By analyzing potential B, CD4+ and CD8+ T cell epitopes, we found that many of these mutations overlap with the predicted epitopes and are frequently present among the 3 HEV genotypes. These overlapping mutations mediate reduced antigenicity. Finally, by delineation of diversification and evolution of the underlying epitopes, we observe that most of these variants apparently evolved earlier in genotype 1 when compared with genotypes 3 and 4. These results indicate that HEV is under substantial evolutionary pressure to develop mutations enabling evasion of the host immune response and resistance to antiviral treatment. This indicates the existence of an ongoing evolutionary arms race between human immunity, antiviral medication and HEV.
| S-EPMC5955438 | biostudies-literature
Project description:AimTo identify the prevalence of pre-S2 start codon mutations and to assess their association with liver disease progression.MethodsThe mutations were identified by direct sequencing from 73 asymptomatic carriers, 66 chronic hepatitis (CH), 66 liver cirrhosis (LC) and 63 hepatocellular carcinoma (HCC) patients. Statistical significances were determined using Fisher's exact test, χ² test, and t-test analyses whenever appropriate. Pre-S mutation as a risk factor for advanced liver disease was estimated by unconditional logistic regression model adjusted with age, sex, and hepatitis B e antigen (HBeAg). P < 0.05 was considered significant.ResultsMutation of the hepatitis B virus (HBV) pre-S2 start codon was found in 59 samples from 268 subjects (22.0%), with higher prevalence in patients with cirrhosis 27/66 (40.9%) followed by HCC 18/63 (28.6%), chronic hepatitis 12/66 (18.2%) and asymptomatic carriers 2/73 (2.7%) (P < 0.001). Logistic regression analysis showed that pre-S2 start codon mutation was an independent factor for progressive liver disease. Other mutations, at T130, Q132, and A138, were also associated with LC and HCC, although this was not statistically significant when adjusted for age, sex, and HBeAg. The prevalence of pre-S2 start codon mutation was higher in HBV/B than in HBV/C (23.0% vs 19.1%), whilst the prevalence of T130, Q132, and A138 mutation was higher in HBV/C than in HBV/B. The prevalence of pre-S2 start codon mutation was higher in LC (38.9%) and HCC (40.0%) than CH (5.6%) in HBeAg⁺ group, but it was similar between CH, LC and HCC in HBeAg⁻ group.ConclusionPre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg⁺ patients.
| S-EPMC3471111 | biostudies-literature
Project description:AIM:To investigate the dynamics of hepatitis C virus (HCV) variability through putative envelope genes during primary infection and the mechanism of viral genetic evolution in infected hosts. METHODS:Serial serum samples prospectively collected for 12 to 34 months from a cohort of acutely HCV-infected individuals were obtained, and a 1-kb fragment spanning E1 and the 5' half of E2, including Thirty-three cloned cDNAs representing each specimen were assessed by a method that combined a single-stranded conformational polymorphism (SSCP) and heteroduplex analysis (HDA) method to determine the number of clonotypes hypervariable region, was amplified by reverse transcriptase PCR and cloned. Nonsynonymous mutations per nonsynonymous site (dn), synonymous mutations per synonymous site (ds), dn/ds ratio and genetic distances within each sample were evaluated for intrahost evolutionary analysis. RESULTS:Quasispecies complexity and sequence diversity were lower in early samples and a further increase after seroconversion, although ds value in the envelope genes was higher than dn value during primary infection. The trend, pronounced in most of samples, toward lower ds values in the E1 than in the 5' portion of E2. Quasispecies complexity was higher and E2 dn/ds ratio was a trend toward higher value in later samples during persistent viremia. We also found individual features of HCV genetic evolution in different subjects who were infected with different HCV genotypes. CONCLUSION:Mutations of actively replicating virus arise stochastically with certain functional constaints. A complexity quasispecies exerted by a combination of either neutral evolution or selective forces shows clear differences in individuals, and associated with HCV persistence.
| S-EPMC4656321 | biostudies-literature
Project description:Duck hepatitis virus (DHV) is one of the commercially important diseases of ducklings worldwide. It is an acute and highly infectious disease of ducklings caused by three different serotypes (1-3) of duck hepatitis A virus (DHAV), and serotype 1 is the most common in poultry. To date, little is known about the prevalence and genetic characterisation of DHAV-1 in Egypt. In the current study, isolation and complete genomic analyses of DHAVs circulating in commercial duck farms in different Egyptian governorates were conducted. A total of eighteen samples were collected from six Egyptian governorates of 3-11 days old ducklings (Pekin and Mullard) with a history of nervous signs and high mortality rates. Five out of eighteen (5/18) samples were screened positive for the DHAV-1 based on the VP1 gene. These samples were individually used for virus isolation in embryonated duck embryos (EDE), followed by complete genome sequencing. Phylogenomic analyses showed that DHAV serotype I; genotype I were diversified into four different groups (1-4). Most of the recent circulating Egyptian DHAV strains are clustered within group 4, while isolates characterised within this study were clustered within group 1. Recombination analyses revealed that the emergence of a new recombinant virus-DHAV-1 strain Egypt-10/2019-through recombination. Likewise, the selective pressure analyses showed the existence, inside or near areas of the viral attachment or related functions, of positive scores highlighting the importance of natural selection and viral evolution mechanism at different protein domains. The findings of this study provide updated information on the epidemiological and genetic features of DHAV-1 strains and underscore the importance of DHAV surveillance as well as re-evaluation for currently used vaccines.
| S-EPMC8472559 | biostudies-literature
Project description:Approximately 20% of patients receiving liver transplants for end-stage hepatitis C rapidly develop severe allograph fibrosis within the first 24 months after transplant. Hepatitis C virus (HCV) variants were studied in 56 genotype-1-infected subjects with end-stage hepatitis C disease at the time before and 12 months after liver transplant, and post-transplant outcome was followed with serial liver biopsies. In 15 cases, pre-transplant HCV genetic diversity was studied in detail in liver (n=15), serum (n=15), peripheral blood mononuclear cells (n=13), and perihepatic lymph nodes (n=10). Our results revealed that pre-transplant HCV genetic diversity predicted the histological outcome of recurrent hepatitis C disease after transplant. Mild disease recurrence after transplant was significantly associated with higher genetic diversity and greater diversity changes between the pre- and post-transplant time points (p=0.004). Meanwhile, pre-transplant genetic differences between serum and liver were related to a higher likelihood of development of mild recurrent disease after transplant (p=0.039).
| S-EPMC2875273 | biostudies-literature
Project description:AimTo identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudine-adefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.MethodsThe patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy, first with lamivudine (LMV) and then, after developing viral breakthrough, with adefovir (ADV) therapy. All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy, which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy. Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy, ADV monotherapy, and LMV-ADV combination therapy. For the genotypic analysis, the whole 1310-bp polymerase gene region was amplified, cloned and sequenced.ResultsAll patients had been previously treated with 100 mg of LMV once daily for a 15- to 26-mo period. The emergence of resistance mutations to LMV, such as rtM204V/I and/or rtL180M, were found in all patients. Their antiviral regimens were switched to ADV monotherapy as the second line treatment. All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy. ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy. The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients. Twenty-seven of 38 clones were combined with an amino acid change at rt181; three clones had mutations in rt236 and one clone had a combined mutation. The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy. Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236. Mutations in rt204 re-emerged during the combination treatment. The rt181 and rt204 mutations did not co-exist in one clone.ConclusionAdd-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.
| S-EPMC3508638 | biostudies-literature