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At least 19 recordsLinked to original sources
PubMed2026

Host-interferon-stimulated gene response to virus-host recombinant variants of hepatitis E virus and enhanced viral replication.

The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. HEV infection can become chronic in immunocompromised individuals, in whom virus-host recombinant variants (VHRVs) can be detected. These variants often harbor host-derived insertions in the polyproline-rich region (PPR), and most display enhanced replication in vitro. However, the mechanisms underlying this replicative advantage remain unclear. It is likely that genes of the infected cells are differentially expressed according to the replicative capacity of the strain. The host factors involved in the improvement of the replicative capacity of these VHRVs are yet to be identified.In this study, we analyzed the host transcriptional response to seven VHRVs in HepG2/C3A cells using bulk RNA sequencing at 48 h and 168 h post-infection. Five VHRVs (RNF19A, ZNF787, KIF1B, RPS17, EEF1A1) previously associated with a high replication rate induced more significant, distinct transcriptomic changes than low-replicative variants (RNA18, RPL6), particularly at 168 h. A shared set of 25 genes, especially interferon-stimulated genes (ISGs), was upregulated in cells infected with high-replicating variants. Interestingly, ISG induction was limited at 48 h despite high viral RNA concentrations, suggesting a delayed antiviral response. At 168 h, high ISG expression coincided with high viral loads, indicating that VHRVs may evade or exploit immune defenses. Our findings reveal candidate ISGs such as IFIT1 and ISG15 that may influence HEV persistence and immune escape. These results offer new insights into the interplay between VHRV replication and host immunity.IMPORTANCEHepatitis E virus (HEV) is a major cause of acute hepatitis and can cause chronic infections in immunocompromised individuals. Virus-host recombinant variants (VHRVs) having integrated host-derived insertions often replicate more effectively, yet the host determinants of this phenotype remain unclear. With RNA sequencing of HepG2/C3A-infected cells, we observed that high-replicating VHRVs induce a delayed but strong expression of interferon-stimulated genes (ISGs), including IFIT1 and ISG15, despite high viral loads. These results suggest that VHRVs may transiently modulate or evade aspects of host antiviral defenses. Our study revealed host transcriptional patterns associated with enhanced viral replication, providing insight into potential mechanisms that enhance HEV replication and highlighting candidate pathways that could influence the interplay between viral replication and immune responses, all requiring further investigation.

Humans↗
PubMed2026

EIF4H and YBX1 are essential host factors for hepatitis E virus replication and pathogenesis.

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Despite the availability of a vaccine in China, no direct-acting antivirals are approved, and host factors required for HEV replication remain poorly defined. Here, using a genome-wide CRISPR/Cas9 knockout screen in a replicon system, we identified Eukaryotic Translation Initiation Factor 4H (EIF4H) and Y-Box Binding Protein 1 (YBX1) as essential host factors for HEV replication and pathogenesis. Knockout of either factor markedly impaired replication of HEV genotypes 1, 3, and 4, as well as HEV infection and production in hepatocellular carcinoma cells and human induced pluripotent stem cell-derived hepatocyte-like cells, while leaving SARS-CoV-2, hepatitis B virus, hepatitis C virus, and Zika virus unaffected, underscoring their HEV-specific roles. Mechanistically, EIF4H interacts with ORF1 via its methyltransferase-Y-papain-like protease region, and EIF4H deficiency alters the composition of the ORF1-associated replication complex. By contrast, YBX1 is dispensable for ORF1 translation and RNA binding but is specifically required for ORF1 proteolytic processing, a prerequisite for assembling a functional replication machinery. EIF4H knockout rats and liver-specific YBX1 knockout rats were largely resistant to rat HEV-C1 infection, showing profound reductions in viral shedding, suppressed hepatic and intestinal viral loads, and protection from liver pathology. Together, our findings establish EIF4H and YBX1 as essential host factors for HEV infection and pathogenesis and reveal potential targets for antiviral intervention.

Virus Replication↗
PubMed2026

The Differential Effects of Immunosuppressants on Hepatitis E Virus Replication and the Triggered Inflammatory Responses in Macrophages.

Organ transplant recipients are at high risk of developing chronic infection when exposed to hepatitis E virus (HEV), which can rapidly progress to liver fibrosis and cirrhosis. Macrophages play a key role in the response to the infection and disease progression. However, the interactions amongst immunosuppressants, macrophages, the course of HEV infection and activation of inflammatory response remain unclear. In this study, we generated M0, M1 and M2 macrophages from the human THP-1 cell line. These macrophages were then infected with HEV and treated with different immunosuppressants. We visualised viral infection using laser confocal microscopy, and quantitatively analysed viral replication and inflammatory responses by bulk sequencing, RT-qPCR, ELISA and Western blotting. We found that the M1 inflammatory macrophages exhibited the highest, while M2 macrophages had the lowest levels of viral RNA. Genome-wide transcriptome analysis indicated that viral, inflammation and immunity-related pathways were predominantly upregulated by HEV infection. Dexamethasone exerted potent inhibitory effects on inflammatory response in macrophages. Mycophenolic acid (MPA) demonstrated inhibitory effects on viral replication, IL-1β and TNF-α expression, whereas mTOR inhibitors had the opposite effects, and tacrolimus showed no clear effect. In conclusion, immunosuppressants can differentially affect HEV replication and the subsequent inflammatory responses in macrophages.

Humans↗
PubMed2025

Genetic characterization of rat hepatitis E virus (Rocahepevirus ratti) in urban brown rats (Rattus norvegicus) in Helsinki, Finland.

We report complete and partial genome sequences of rat hepatitis E virus (RHEV, Rocahepevirus ratti), from archived brown rats captured in Helsinki, Finland. Phylogenetic analysis confirmed the presence of the pathogenic RHEV genotype C1 in the Helsinki region. Finnish strains clustered together with strains from South Korea and Spain. However, the polytomous topology of phylogenetic trees and the large genetic distances between spatially distinct strains suggest that RHEV has remained inadequately sampled on a global scale. Further surveillance of rocahepeviruses is needed to assess their threat to public health and to understand their diversity and evolutionary patterns.

Animals↗
PubMed1977

Prognostic implications of the e antigen of hepatitis B virus.

The e antigen HBeAg and its antibody anti-HB, have been said to be predictive of chronicity and resolution, respectively, in viral hepatitis. We found, as have others, a specific association with hepatitis B virus-induced disease. In addition, detectability of HBeAg in the acute phase of type B hepatitis was followed by a sixfold higher incidence of chronic hepatitis. Unfortunately, the prediction was erroneous in 65% of positive cases and 6% of negative cases. In chronic hepatitis, HBeAg did not necessarily disappear in advance of resolution, and its disappearance did not necessarily indicate resolution. Two patients with acute hepatitis progressing to chronicity were anti-HBe-positive in both phases, as were seven (5%) with chronic hepatitis. For individual patients, therefore, HBeAg and anti HBe are not prognostically useful indexes.

Acute Disease↗
PubMed2026

Whole-Genome Analysis of HEV Under Sequential Ribavirin Pressure Reveals Early Minor Variants Predicting Resistance.

Ribavirin (RBV) failures in chronic hepatitis E virus (HEV) infection may arise from genomic adaptation, yet the contribution of minor variants remains insufficiently explored. Using a shotgun metagenomics based on next-generation sequencing to obtain the full HEV genome, we analyzed longitudinal HEV populations from sequential clinical samples collected from a patient infected by Paslahepevirus balayani genotype 3c, who underwent three different courses of RBV treatment. Viral diversity increased over time, with most amino-acid substitutions detected at sub-consensus frequencies. Several mutations linked to RBV resistance emerged under treatment pressure. Specifically, D1384N and Y1587F became fixed in the final sampling, while additional substitutions at position 1384 (including D1384T) revealed mutational hotspot. Importantly, D1384N and G1634R were already detectable at low allele frequencies after the first treatment cessation and subsequent rebound, showing that the study of minor variant populations can be early predictors for the development of RBV resistance. These findings underscore the genomic plasticity of HEV under antiviral pressure and highlight the value of deep variant profiling for anticipating RBV treatment failure.

Ribavirin↗
PubMed1976

Relation of e antigen to hepatitis B virus infection in an area of hyperendemicity.

A study of the e determinant of hepatitis B surface antigen in an area of hepatitis B hyperendemicity revealed that the presence of e antigen or of antibody to e in the sera of individuals was specifically related to evidence of past or present infection with hepatitis B virus. Among asymptomatic long-term carriers of hepatitis B surface antigen, presence of the e antigen was associated with elevated levels of aspartate and alanine aminotransferases in serum; this observation suggested that the e antigen might be a marker for persisting hepatic dysfunction. Higher levels of DNA polymerase found in carriers of the surface antigen with e antigen suggested that these individuals might have a higher level of circulating Dane particles and thus, perhaps, a higher level of hepatitis B virus infectivity.

Adolescent↗
PubMed1978

Full and empty Dane particles in chronic hepatitis B virus infection: relation to hepatitis B e antigen and presence of liver damage.

Circulating complete and defective hepatitis B virus forms, as represented by full, DNA polymerase-positive and empty, DNA polymerase-negative Dane particles, respectively, were investigated in sera from patients with chronic hepatitis B virus infection and related to the presence of e antigen and antibody and to the histological findings on liver biopsy. Complete hepatitis B virus particles were detected in the serum of all patients postive for e antigen, their percentage ranging from 15 to 61% of the total Dane particle population. Although most of these cases had chronic persistent or chronic active hepatitis, complete viral particles were also found in serum of 3 healthy carriers of hepatitis B surface antigen who had e antigen. These results indicate that e antigen is a marker of active virus replication and support its association with infectivity. It is also associated with liver damage because production of complete virus is a feature of chronic hepatitis. In the presence of anti-e, detection of Dane particles in serum appeared to be related to the histological findings. Most of the healthy carriers had no Dane particles in serum, whereas 80% of the cases with chronic liver disease had circulating Dane particles. However, in contrast to the cases with e antigen, 98 to 100% of Dane particles in these cases appeared to be defective in nucleic acid material on electron microscopy after positive staining. All of the patients with chronic active hepatitis in this group had progressed to cirrhosis and it is possible that production of complete virus particles is reduced in the later stages of the illness.

Carrier State↗
PubMed1978

Duality of hepatitis B e antigen in serum of persons infected with hepatitis B virus: evidence for the nonidentity of e antigen with immunoglobulins.

Hepatitis B e antigen (HBeAg) is detected in the serum of some persons infected with hepatitis B virus. Owing to a close correlation of HBeAg and hepatitis B virus in the serum, it has been used as a practical indicator of infectivity. Two entities of HBeAg activity physicochemically different from each other were demonstrated in the serum of persons infected with hepatitis B virus. One was associated with a molecule that precipitated in 1.33 M ammonium sulfate solution, was larger than IgG, and had an electrophoretic mobility in the beta- to gamma-globulin regions and an isoelectric point of approximately pH 5.7. In contrast, the other HBeAg activity was associated with a molecule that was soluble in 1.33 M ammonium sulfate solution, was smaller than IgG, and had an electrophoretic mobility in the alpha-globulin region and an isoelectric point at pH 4.8. In spite of their marked physicochemical differences, a line of antigenic identity was clearly observed for them when they were tested against antibody to HBeAg by a them when they were tested against antibody to HBeAg by a double immunodiffusion method. The HBeAg activity associated with the large molecule was completely removed by an affinity column of anti-IgG, whereas the activity of the small molecule was not. These results indicate that, in the serum, HBeAg exists as a molecule smaller than IgG and also in association with IgG.

Electrophoresis, Disc↗
PubMed1978

e Antigen in hepatitis B virus infected dialysis patients: assessment of its prognostic value.

Many investigations consider the presence of e antigen (HBeAg) valuable in predicting which patients with acute hepatitis B are at risk of remaining infected and developing chronic liver disease. We tested this hypothesis in a retrospective study of serial samples from patients undergoing long-term hemodialysis. We found HBeAg in the early phase of all hepatitis B virus (HBV) infections. There was no significant difference between transiently and persistently hepatitis B surface antigen (HBsAg)-positive persons with regard to the frequency of HBeAg during the first 3 months of HBs antigenemia. Thus during the early period of viral activity, the presence of HBeAg is of no prognostic values in determining chronicity of HBV infection. We believe the disagreement on the prognostic value of HBeAg is a reflection of variations in time and frequency of sampling. The HBeAg remains, however, a useful indicator of potential infectivity of HBsAg(+)persons.

Chronic Disease↗
PubMed1979

Shift from free "small" hepatitis B e antigen to IgG-bound "large" form in the circulation of human beings and a chimpanzee acutely infected with hepatitis B virus.

Hepatitis B e antigen (HBeAg) occurs both free and in association with IgG in the circulation of individuals infected with hepatitis B virus (HBV). We determined free and IgG-bound HBeAg forms separately in the serum of humans and a chimpanzee acutely infected with HBV. In a patient with laboratory acquired HBV infection, the proportion of free HBeAg gradually decreased from 89% to 23%. A similar shift from free to IgG-bound form of HBeAg was invariably observed in 5 additional patients with acute Type B hepatitis. In a chimpanzee that had been experimentally inoculated with HBV, free HBeAg appeared first, then gradually and completely shifted to the IgG-bound form. Finally, IgG-bound HBeAg disappeared, and antibody to HBeAg was detectable in the serum. The determination of both free and IgG-bound forms of HBeAg may provide valuable information, because their ratio reflects the stage and prognosis of acute HBV infection.

Acute Disease↗
PubMed1979

Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.

The complete nucleotide sequence of hepatitis B virus genome (subtype ayw) cloned in Escherichia coli has been determined using the Maxam and Gilbert method and the dideoxynucleotide method. This sequence is 3,182 nucleotides long. Location of the nonsense codons shows that the coding capacity of the L chain is larger than the coding capacity of the S chain. Eight open regions, able to code for polypeptide chains larger than 100 amino acids, have been located. Region 6, which is the largest, covers more than 80% of the genome. The gene S which codes for polypeptide I of the Hbs Ag and was previously located between coordinates 95.1 and 73.6 is contained in region 7.

Base Sequence↗
PubMed1979

Hepatitis B virus genes and their expression in E. coli.

A composite DNA sequence of regions of hepatitis B virus, determined from a series of recombinant plasmids, reveals the genes for the surface antigen and the core antigen of the virus. The sequence of the core antigen shows it to be a DNA binding protein. The core antigen gene is expressed in Escherichia coli and when injected into rabbits the bacterial product induces antibodies which react with core antigen isolated from human sources.

Amino Acids↗
PubMed1979

Hepatic infections. Part II. The effect of acute and chronic hepatitis B antigenaemia on the reaction to antibodies to sheep red cells (microbial antigens) and human T-activated cells (exposed autologous tissue antigens).

Using the agglutination of sheep red cells by human antibodies as an indicator of microbial antibody activity, a highly significant association was found between the response to the e antigen of the hepatitis B virus and the formation of strong antibody levels to microbial substances (chi 2(1) = 33). This kind of association was not found among chronic carriers of the hepatitis B virus who do not produce antibodies to the e antigen (chi 2(1) = 3,7). In the presence of e antigen activity, patients with acute virus B hepatitis almost always show significantly reduced levels of antibodies to microbial substances (chi 2(1) = 20). The findings indirectly reveal that e activity is associated with the inability of the liver to trap bacterial antigens. Circumstantial evidence further suggests that the e factor may bear antigens on its immunoglobulin-like structure very similar to microbial cell wall components. Accepting that human antibodies to the T (Thomsen-Friedenreich) antigen represent reactions to cryptantigenic membrane structure of autologous tissues, it was significant to record that increased anti-t activity is always demonstrated when virus B infections progress from the acute to the chronic carrier stage (chi 2(1) = 73). The most intense anti-T activity is commonly found in subjects who produce antibodies to the hepatitis B surface antigen (chi 2(1) = 138). In the presence of e antigen the amount of anti-T in circulation is always significantly depressed. Since this type of depression is not seen in patients with acute virus B hepatitis who lack the e antigen, we suspect that the reduced anti-T levels in e antigen-positive patients are linked with the in vivo exposure of T receptors by microbial neuraminidase.

Acute Disease↗
PubMedDate not supplied

Studies on the active principles of Schisandra sphenanthera Rehd. et Wils. The structures of schisantherin A, B, C, D, E, and the related compounds.

Deoxyschisandrin (VIII) and five new lignans, named schisantherin A, B, C, D, and E, were isolated from the active fraction of the fruits of Schisandra sphenanthera Rehd. et Wils. Their configurations and conformations were established by exhaustive spectral analysis as well as chemical degradations as shown in Ia, Ib; IIa, IIb; IIIa, IIIb; IVa, IVb, and Va, Vb respectively, and their absolute configurations at biphenyl, at C6, C7, and C8 were all assigned to be S form. The position of the methylenedioxyl group in the structures of gamma-schisandrin and Wuweizisu C (as described in the literature), isolated from Schisandra chinensis, must be corrected as shown in VI and VII respectively. In pharmacologica studies and preliminary clinical trials, schisantherin A, B, C, and D showed good effect in lowering the serum glutamic-pyruvic transaminase level of the patients suffering from chronic virus hepatitis. Schisantherin E and deoxyschisandrin were not effective.

Animals↗