An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies.
Ontology highlight
ABSTRACT:
SUBMITTER: Fatehi F
PROVIDER: S-EPMC8786976 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best.
| S-EPMC7823939 | biostudies-literature
Project description:The potential impact of increasing test-and-treat coverage on hepatitis B virus (HBV) infection remains unclear in China. The objective of this study was to develop a dynamic compartmental model at a population level to estimate the long-term effect of this strategy.Based on the natural history of HBV infection and 3 serosurvey data of hepatitis B in China, we proposed an age- and time-dependent discrete model to predict the number of new HBV infection, the number of chronic HBV infection, and the number of HBV-related deaths for the time from 2018 to 2050 under 5 different test-and-treat coverage and compared them with current intervention policy.Compared with current policy, if the test-and-treat coverage was increased to 100% since 2018, the numbers of chronic HBV infection, new HBV infection, and HBV-related deaths in 2035 would be reduced by 26.60%, 24.88%, 26.55%, respectively, and in 2050 it would be reduced by 44.93%, 43.29%, 43.67%, respectively. In contrast, if the test-and-treat coverage was increased by 10% every year since 2018, then the numbers of chronic HBV infection, new HBV infection, and HBV-related deaths in 2035 would be reduced by 21.81%, 20.10%, 21.40%, respectively, and in 2050 it would be reduced by 41.53%, 39.89%, 40.32%, respectively. In particular, if the test-and-treat coverage was increased to 75% since 2018, then the annual number of HBV-related deaths would begin to decrease from 2018. If the test-and-treat coverage was increased to above 25% since 2018, then the hepatitis B surface antigen (HBsAg) prevalence for population aged 1 to 59 years in China would be reduced to below 2% in 2035. Our model also showed that in 2035, the numbers of chronic HBV infection and HBV-related deaths in 65 to 69 age group would be reduced the most (about 1.6 million and 13 thousand, respectively).Increasing test-and-treat coverage would significantly reduce HBV infection in China, especially in the middle-aged people and older people. The earlier the treatment and the longer the time, the more significant the reduction. Implementation of test-and-treat strategy is highly effective in controlling hepatitis B in China.
| S-EPMC5916706 | biostudies-literature
Project description:MicroRNAs (miRNAs) are short sequences of noncoding single-stranded RNAs that exhibit inhibitory effects on complementary target mRNAs. Recently, it has been discovered that certain viruses express their own miRNAs, while other viruses activate the transcription of cellular miRNAs for their own benefit. This review summarizes the viral and/or cellular miRNAs that are transcribed during infection, with a focus on the biomarker and therapeutic potential of miRNAs (or their antagomirs). Several human viruses of clinical importance are discussed, namely, herpesviruses, polyomaviruses, hepatitis B virus, hepatitis C virus, human papillomavirus, and human immunodeficiency virus.
| S-EPMC4718089 | biostudies-literature
Project description:The hepatitis A virus cellular receptor 1 (HAVCR1) gene is highly polymorphic, and several variants have been associated with susceptibility to allergic and autoimmune diseases. The HAVCR1 gene region was identified as a candidate for hepatitis C virus (HCV) natural clearance in a genotyping study of selected immune response genes in both European-American and African-American populations. The aim of the present study was to explore the influence of HAVCR1 in the outcome of HCV infection in the Spanish population. Three cohorts, consisting of 354 subjects with persistent HCV infection (285 with persistent HCV monoinfection and 69 with natural clearance), 182 coinfected HIV/HCV patients, and 320 controls, were included. Samples were genotyped in several polymorphic positions, insertion/deletion variants in exon 4 and tag single nucleotide polymorphisms (SNPs), in order to define previously described HAVCR1 haplotypes (haplotypes A to D). No statistically significant differences were observed with spontaneous resolution of infection or with viral clearance after treatment. Nevertheless, different rates of infection by viral genotypes (G's) were observed among the HAVCR1 haplotypes. Individuals bearing haplotype C had the highest viral G1 infection rate when compared to individuals bearing other haplotypes (75.82% versus 57.72%, respectively; corrected P value [P(c)], 3.2 × 10(-4); odds ratio [OR], 2.30; 95% confidence interval [CI], 1.51 to 3.47). Thus, HAVCR1 could be involved in susceptibility or resistance to infection by a particular HCV genotype.
| S-EPMC3272938 | biostudies-literature
Project description:Hepatitis B virus (HBV) chronically infects over 250 million people worldwide and causes nearly 1 million deaths per year due to cirrhosis and liver cancer. Approved treatments for chronic infection include injectable type-I interferons and nucleos(t)ide reverse transcriptase inhibitors. A small minority of patients achieve seroclearance after treatment with type-I interferons, defined as sustained absence of detectable HBV DNA and surface antigen (HBsAg) antigenemia. However, type-I interferons cause significant side effects, are costly, must be administered for months, and most patients have viral rebound or non-response. Nucleos(t)ide reverse transcriptase inhibitors reduce HBV viral load and improve liver-related outcomes, but do not lower HBsAg levels or impart seroclearance. Thus, new therapeutics are urgently needed. Lambda interferons (IFNLs) have been tested as an alternative strategy to stimulate host antiviral pathways to treat HBV infection. IFNLs comprise an evolutionarily conserved innate immune pathway and have cell-type specific activity on hepatocytes, other epithelial cells found at mucosal surfaces, and some immune cells due to restricted cellular expression of the IFNL receptor. This article will review work that examined expression of IFNLs during acute and chronic HBV infection, the impact of IFNLs on HBV replication in vitro and in vivo, the association of polymorphisms in IFNL genes with clinical outcomes, and the therapeutic evaluation of IFNLs for the treatment of chronic HBV infection.
| S-EPMC8230240 | biostudies-literature
Project description:Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-alpha and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection.
| S-EPMC2217617 | biostudies-other
Project description:BackgroundThe epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology.MethodsSerum samples from 1379 individuals, aged 5-75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years.ResultsA rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children < 6-years.ConclusionsOur study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies.
| S-EPMC7477833 | biostudies-literature
Project description:BackgroundGymnosporangium asiaticum and G. yamadae can share Juniperus chinensis as the telial host, but the symptoms are completely different. The infection of G. yamadae causes the enlargement of the phloem and cortex of young branches as a gall, but not for G. asiaticum, suggesting that different molecular interaction mechanisms exist the two Gymnosporangium species with junipers.ResultsComparative transcriptome analysis was performed to investigate genes regulation of juniper in responses to the infections of G. asiaticum and G. yamadae at different stages. Functional enrichment analysis showed that genes related to transport, catabolism and transcription pathways were up-regulated, while genes related to energy metabolism and photosynthesis were down-regulated in juniper branch tissues after infection with G. asiaticum and G. yamadae. The transcript profiling of G. yamadae-induced gall tissues revealed that more genes involved in photosynthesis, sugar metabolism, plant hormones and defense-related pathways were up-regulated in the vigorous development stage of gall compared to the initial stage, and were eventually repressed overall. Furthermore, the concentration of cytokinins (CKs) in the galls tissue and the telia of G. yamadae was significantly higher than in healthy branch tissues of juniper. As well, tRNA-isopentenyltransferase (tRNA-IPT) was identified in G. yamadae with highly expression levels during the gall development stages.ConclusionsIn general, our study provided new insights into the host-specific mechanisms by which G. asiaticum and G. yamadae differentially utilize CKs and specific adaptations on juniper during their co-evolution.
| S-EPMC10077639 | biostudies-literature
Project description:Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3 (IRF-3) and the host IFN-alpha/beta response that limits virus infection. The hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling, but how this regulation controls the host response to HCV is not known. Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo. Here, we show that HCV infection transiently induces RIG-I- and IPS-1-dependent IRF-3 activation. This host response limits HCV production and constrains cellular permissiveness to infection. However, HCV disrupts this response early in infection by NS3/4A cleavage of IPS-1 at C508, releasing IPS-1 from the mitochondrial membrane. Cleavage results in subcellular redistribution of IPS-1 and loss of interaction with RIG-I, thereby preventing downstream activation of IRF-3 and IFN-beta induction. Liver tissues from chronically infected patients similarly demonstrate subcellular redistribution of IPS-1 in infected hepatocytes and IPS-1 cleavage associated with a lack of ISG15 expression and conjugation of target proteins in vivo. Importantly, small-molecule inhibitors of NS3/4A prevent cleavage and restore RIG-I signaling of IFN-beta induction. Our results suggest a dynamic model in which early activation of IRF-3 and induction of antiviral genes are reversed by IPS-1 proteolysis and abrogation of RIG-I signaling as NS3/4A accumulates in newly infected cells. HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice.
| S-EPMC1458687 | biostudies-literature
Project description:AIM:To investigate the prevalence of hepatitis G virus (HGV) infection and to analyse the homology of different HGV strains in Southern China. METHODS:A total of 1993 sera from different groups in Guangdong, Hong Kong, and Yunnan were detected by reverse transcription polymerase chain reaction (RT-PCR). The nucleotide sequences of 5'untranslated region (5'UTR) derived from 20 strains and NS5 region from 3 strains were determined. RESULTS:The positive rate of HGV RNA was 0.89 % in community population, 2.57 % in blood donors, 17.86 % in intravenous drug abusers, 14.13 % in patients with hemodialysis, 13.66 % in those with hepatocellular carcinoma, 25.30 % in non A-E hepatitis, 7.22 % in hepatitis B, 12.73 % in hepatitis C, 41.67 % in patients received bone marrow transplantation, respectively. The homology was 90.40-100 % in 5'UTR among different strains, while that of NS5 region was 93.3-94 % in nucleotide sequence, and 97-99.2 % in amino acid sequence. CONCLUSION:These results showed that there was a high incidence of HGV infection in patients from Southern China, being treated for bone marrow transplantation, hepatocellular carcinoma and those on haemodialysis. Furthermore, there was also a high frequency of co-infection of HGV with HBV, HCV, non A-E viral hepatitis and that among intravenous drug abusers. The study also showed that sequence variation in different strains was associated with geographical factors but there was no significant difference in 5'UTR in circulating viruses between different patient groups. Finally, by sequential analysis of viral species present in individual patients over a three months period there was no evidence of sequence variation in the 5' UTR.
| S-EPMC4656385 | biostudies-literature