Search Results (1,904)

Background: Hepatitis D virus (HDV) causes one of the most severe forms of chronic viral hepatitis. Despite its severity, universal screening of hepatitis B surface antigen (HBsAg)-positive individuals, as recommended by European guidelines, is not widely implemented. This study aimed to evaluate the yield of reflex HDV testing and to characterize HBV carriers who tested positive or negative for anti-HDV. Methods: A retrospective cohort study was conducted using the Clalit Health Services database in northern Israel (2014–2024). HBsAg-positive patients were categorized into two groups: those screened for HDV via reflex testing (2019–2024) and those tested based on clinical discretion (2014–2019). We compared these cohorts to evaluate the impact of reflex screening on coverage, diagnostic yield, and time to diagnosis. Results: Among 1336 HBsAg-positive individuals, HDV screening rates increased from 57.5% to 93.1% following reflex implementation. HDV seropositivity increased from 3.17% to 6.48% (p = 0.02). Ethiopian-born individuals had significantly higher positivity than others (10.4% vs. 3.9%, p = 0.0221). The average time from HBV diagnosis to HDV testing decreased from 38.1 ± 31 months (median 37.5) to 1.3 ± 6.1 months (median 0). Conclusions: Anti-HDV reflex testing significantly improved screening coverage, increased detection of anti-HDV seropositive cases and was associated with shorter time to serologic identification. These findings support the integration of reflex testing into national screening policies to enable earlier diagnosis and reduce the burden of infection. Full article

Viral infections of the central nervous system produce memory impairment through mechanisms that extend beyond acute neuronal injury. Herpes simplex virus type 1, human immunodeficiency virus, varicella zoster virus, cytomegalovirus, Epstein–Barr virus, influenza, SARS-CoV-2, West Nile virus, and Zika virus each enter or engage the brain through distinct routes, yet converge on four shared molecular pathways that selectively damage hippocampal circuits: mitochondria-associated membrane (MAM) dysfunction, chronic neuroinflammation, blood–brain barrier (BBB) disruption, and impaired CREB-BDNF signaling. These pathways specifically compromise the dentate gyrus, CA3, and CA1 subfields, producing predictable deficits in pattern separation, associative retrieval, and temporal memory binding. Antiretroviral and antiviral therapies suppress viral replication but fail to reverse organelle-level dysfunction, leaving most hippocampal injury unaddressed. Emerging plasma biomarkers, p-tau217, neurofilament light chain, and GFAP, combined with hippocampal subfield MRI, now enable mechanistic stratification before irreversible circuit loss occurs. This review proposes, as a unifying hypothesis, that virus-associated memory impairment represents a convergent hippocampal syndrome driven by shared downstream pathways, and that combination therapies targeting these pathways simultaneously offer greater therapeutic promise than pathogen-specific approaches alone. The evidentiary basis for this framework varies across pathogens and conditions; direct mechanistic evidence, mechanistic analogy, and preclinical data are distinguished throughout. Full article

Background and Aims: Understanding regulatory interactions between hepatitis B virus (HBV) and host factors is essential for the development of next generation host-directed antiviral therapies and the achievement of a functional HBV cure. Here, we investigated HBV-induced alterations in host gene expression in primary human hepatocytes (PHH) to identify host factors exploited by the virus for replication and persistence. Whole-transcriptome sequencing (WTS) of HBV-infected PHH identified host pathways with potential roles in the HBV life cycle. RNA interference-based functional screening of dysregulated candidate genes identified cyclin L1 (CCNL1) as a key host factor. RNAi-mediated knockdown of CCNL1 reduced HBV gene expression, including hepatitis B surface antigen (HBsAg). Mechanistically, CCNL1 regulates phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) at serine 2 (S2), consistent with a role in transcriptional regulation. CCNL1 knockdown further reduced the binding of total and phospho- (Ser2/Ser5) RNAPII, pan-acetylated histone H3 (H3ac), and H3K27ac to HBV covalently closed circular DNA (cccDNA), indicating impaired cccDNA-dependent transcription. In addition, CCNL1 expression was elevated in chronic hepatitis B patients compared with those with resolved infection. Collectively, these data demonstrate that CCNL1 promotes HBV transcription and replication through modulation of RNAPII phosphorylation and chromatin-associated transcriptional activity, identifying CCNL1 as a potential host susceptibility factor for HBV. Importance: Hepatitis B virus infection remains a major threat to human health in areas with high prevalence. There is need to fully understand the complex interactions between the virus and human host factors/processes to support ongoing efforts to develop anti-HBV therapies that can be used with existing therapies to achieve a better cure. HBV relies on host cellular factors and biological processes to establish and maintain efficient infection, making host–virus interactions attractive targets for therapeutic intervention. Thus, identifying host factors that support and/or restrict HBV infection is essential for understanding the molecular basis of chronic HBV infection and for developing host-targeting anti-HBV drugs. This study identifies cyclin L1 (CCNL1) as a host susceptibility factor that promotes HBV transcription and replication through regulation of RNA polymerase II activity and or post-transcriptional mechanisms. Full article

Hepatitis E virus (HEV) is an emerging zoonotic pathogen of increasing concern in developed regions and represents a major cause of acute viral hepatitis worldwide, primarily transmitted via the fecal–oral route. Although most infections are self-limiting, immunocompromised individuals, such as people living with human immunodeficiency virus (PLWH) and pregnant women, are at risk of severe outcomes, including chronic infection and fatal liver failure, respectively. This study was aimed at evaluating the prevalence and genetic diversity of HEV in PLWH and relevant ecological niches (swine and wastewater) in Venezuela. A total of 417 serum samples from PLWH, 85 wastewater samples, and 67 swine fecal samples were tested for serological or molecular HEV markers. The seroprevalence of anti-HEV antibodies among PLWH was 0.2% for IgM and 5.5% for IgG. HEV RNA was not detected in samples from PLWH or wastewater; however, a 1.5% prevalence of active infection was identified in swine. Phylogenetic analysis of a complete HEV genome revealed an unassignable subtype within genotype 3, tentatively designated as 3p. To the best of our knowledge, this study provides the first molecular characterization and report on HEV frequency in PLWH, wastewater, and swine in Venezuela. Full article

Hepatitis B virus (HBV) remains a leading cause of chronic liver disease worldwide, contributing to cirrhosis and hepatocellular carcinoma. Sub-Saharan Africa accounts for an estimated 68% of incident HBV infections, where co-infection with human immunodeficiency virus (HIV) is common and associated with poorer clinical outcomes. In Botswana, limited HBV screening and the absence of established HBV management guidelines persist despite reported HIV-HBV co-infection rates ranging from 1.1% to 10.6%. This scoping review aimed to summarise existing research on HBV and HIV-HBV co-infection in Botswana and assess clinical and policy implications. Following PRISMA methodology, searches were conducted across PubMed, Google Scholar, Semantic Scholar, and Consensus databases. Thirty eligible peer-reviewed studies were identified and evaluated for prevalence data, virological characteristics, genotypes, mutations, treatment outcomes, vaccination programs, and the availability of guidelines. Findings indicate intermediate-to-high HBV and HIV-HBV disease burden, substantial occult HBV infection, and gaps in diagnostic and preventive practices. The lack of routine screening, deficient infant birth-dose and adult vaccination, and established treatment pathways likely increase the risk of HBV-associated morbidity and mortality. Strengthened public health interventions, including expanded testing, enhanced vaccination coverage, and prevention of mother-to-child transmission strategies, are recommended to improve disease control and clinical outcomes in Botswana. Full article

Background/Objectives: Sarcopenia and impaired bone quality are increasingly recognized as important determinants of outcomes after liver transplantation (LT). However, longitudinal data describing early post-transplant musculoskeletal changes in patients with chronic hepatitis B virus (HBV) infection, particularly according to hepatocellular carcinoma (HCC) status, remain limited. Aim: To evaluate longitudinal changes in skeletal muscle mass and vertebral bone attenuation after LT in patients with chronic HBV infection and to assess the impact of concomitant HCC and clinical subgroups on these patterns. Methods: This retrospective, single-center study included 99 adult patients who underwent LT for chronic HBV infection (HBV alone, n = 59; HBV + HCC, n = 40) between January 2018 and December 2024. Contrast-enhanced abdominal computed tomography examinations obtained before transplantation and at approximately 6 (POD180) and 12 months (POD365) after transplantation were analyzed. Skeletal muscle was assessed using psoas muscle area (PMA) and psoas muscle index (PMI), while bone quality was evaluated using mean vertebral trabecular attenuation averaged across L1–4. Longitudinal changes were examined according to HCC status, sex, Child–Pugh class, and survival status. Results: Repeated-measures analyses of longitudinal changes demonstrated a significant decline in both PMA and PMI at POD180 and POD365 compared with pre-transplant values (PMA: p = 0.006; PMI: p = 0.009). These patterns were comparable between patients with HBV alone and those with HBV-related HCC, with no significant differences between groups (all p > 0.05). Male patients consistently exhibited higher PMA and PMI values than female patients across all assessed time points (both p < 0.001). In contrast, neither Child–Pugh class nor mortality status was associated with differences in PMA or PMI levels (all p > 0.05). L1–4 attenuation declined markedly by POD180 and remained below baseline at POD365 (p < 0.001). Although overall L1–4 values did not differ between disease groups (p = 0.109), the temporal pattern of L1–4 change differed according to survival status (p = 0.026), with a greater decline observed in non-survivors. Conclusions: In patients with chronic HBV undergoing LT, early post-transplant loss of skeletal muscle and vertebral bone attenuation is common and persists throughout the first year of follow-up. These changes occur similarly in patients with and without HCC. CT-based assessment of muscle and bone parameters, particularly L1–4 attenuation, may therefore support early post-transplant risk stratification. Full article

The presence of human herpesviruses is frequently detected in the oral cavity, yet their disease-specific role in chronic inflammatory oral mucosal disorders remains uncertain. This comparative observational study investigated Epstein–Barr virus (EBV) and human herpesvirus-7 (HHV-7) genomic sequences in saliva and virus-specific antibodies in serum among patients with oral lichen planus (OLP; n = 35), aphthous stomatitis (AS; n = 31), and healthy controls (n = 34). Salivary viral loads were quantified using real-time PCR, while EBV and HHV-7-specific IgG and IgM antibodies were measured using ELISA-based assays. EBV and HHV-7 DNA in saliva were commonly detected across all groups, demonstrating high baseline shedding and marked interindividual variability. Although EBV IgG levels were higher in OLP compared with AS in univariate analysis, multivariate regression revealed that age, rather than disease status, was the primary determinant of EBV IgG levels. After adjustment for age, sex, and discomfort, neither EBV nor HHV-7 salivary loads showed independent associations with OLP or AS. HHV-7 salivary loads were uniformly distributed among groups. These findings suggest that salivary detection of EBV and HHV-7 reflects widespread latent infection rather than disease-specific activity in OLP or AS. Longitudinal and tissue-based studies integrating immunological profiling are warranted to clarify whether herpesvirus reactivation contributes to disease severity in defined patient subgroups. Full article

Hepatitis B virus (HBV) is the smallest partially double-stranded, reverse-transcribing DNA virus, with four open reading frames (ORFs) encoding viral proteins. It is classified into nine geographically distributed genotypes (A–I). In Kenya, the molecular characterization of HBV among patients seeking medical care remains poorly defined. This observational study aimed to characterize HBV among patients seeking medical care in Kenya’s endemic region, focusing on circulating genotypes and ORF mutations. Serum samples were collected from the outpatient departments of selected health facilities, with demographic and clinical information extracted from patients’ medical records. Hepatitis B surface antigen (HBsAg) was tested at the facilities, and 85 HBsAg-positive samples were collected for molecular analysis. The basal core promoter and pre-core (BCP/PC), polymerase, and surface regions of the viral genome were amplified and sequenced to determine genotypes and to profile their mutations. Out of 85 HBsAg-positive samples, 38 samples tested positive for HBV DNA, and 26 samples were successfully sequenced. HBV genotype A was prevalent at 73.1% (19/26), followed by genotype D at 23.1% (6/26), and genotype E at 3.8% (1/26). Genotype A sequences clustered with both A1 Asian and African subgenotypes, whereas genotype D clustered with subgenotypes D6 and D1. All HBV genotype A, D, and E sequences were serotypes adw2, ayw2, and ayw4, respectively. HBV core promoter mutations (A1762T/G1764A) were detected in both genotype D and genotype A isolates. The pre-core G1896A mutation was highly prevalent in genotype D samples (5/6; 83.3%) but was not observed in genotypes A or E. Analysis of mutations within the “a” determinant region revealed genotype-specific patterns: genotype A predominantly harbored V14A, P46H, S58C, and P67Q substitutions; genotype E showed N59S; and genotype D exhibited V14A, C69stop, S104T, and W182stop mutations. Two drug resistance mutations (V191I and A194T) were present in two chronic patients, one with genotype A and the other with genotype D. In conclusion, HBV genotypes A and D are the most prevalent among Kenyan patients with chronic HBV infection. The presence of point mutations in the ORFs among patients seeking medical care highlights the need for molecular surveillance to better understand the viral diversity and its potential clinical and public health implications. Full article

SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with onset typically in early adulthood and the potential for long-term disability. Current therapies are initiated after symptom onset and do not address early disease triggers, highlighting the need for preventive strategies. Epstein–Barr virus (EBV) infection has emerged as the strongest candidate upstream factor in MS development. This narrative review provides a focused and critical synthesis of current evidence, with particular emphasis on the prevention perspective and the conceptual framing of MS as a potentially infection-driven disease. We integrate epidemiological, immunological, and mechanistic data while explicitly addressing key uncertainties and limitations in causal interpretation. Longitudinal studies indicate that EBV infection precedes MS onset in most cases and is associated with a markedly increased risk following seroconversion. However, EBV infection alone is not sufficient to cause MS. Proposed mechanisms include immune dysregulation and molecular mimicry, though key uncertainties remain. Based on current evidence, EBV represents a promising but unproven target for MS prevention. Future strategies may include prevention of EBV infection or infectious mononucleosis, alongside improved risk stratification and long-term studies to assess the impact of EBV-targeted interventions on MS incidence. Full article

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4⁺ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry (n = 3–5 per group) and RNA-seq (n = 13), focusing on CADM1^highCD4⁺ T cells enriched for HTLV-1-infected cells to evaluate a transferrin receptor (TfR)-expressing subset. TfR⁺CADM1^highCD4⁺ T cells were detected in both asymptomatic carriers and patients with HAM, but their frequency among CD4⁺ T cells was higher in HAM patients. These cells exhibited a Treg-like phenotype with higher Foxp3 and CTLA-4 expression than TfR⁻ cells and showed increased Ki-67 positivity, consistent with proliferation. Despite this phenotype, they produced interferon-γ, indicating inflammatory potential, while Foxp3 expression was lower in HAM patients than in asymptomatic carriers, suggesting a more inflammatory phenotype. Furthermore, TfR transcript levels (RNA-seq TPM) correlated with clinical indicators of disease activity, including neopterin and CXCL10 protein levels, and the Osame motor disability score. Collectively, these findings suggest that TfR identifies a proliferative, Foxp3-low, Treg-like inflammatory CD4⁺ T-cell subset that is associated with disease activity in HAM. Full article

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance. Full article

Hepatitis C virus (HCV) infection is a global health concern, chronically affecting over 71 million people. It primarily targets the liver but also causes systemic complications through inflammation, oxidative stress, and metabolic dysregulation. HCV is a highly variable RNA virus with six major genotypes that are mainly transmitted via blood. Often asymptomatic, the infection progresses silently to chronic hepatitis C (CHC), which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have revolutionized treatment, achieving cure rates above 95%, improving liver function, reversing fibrosis, and normalizing metabolism. HCV disrupts iron metabolism by suppressing hepcidin, causing iron overload and oxidative stress. It also alters lipid metabolism, inducing steatosis, and affects glucose metabolism, contributing to insulin resistance and type 2 diabetes. DAAs improve these metabolic outcomes. HCV promotes oxidative stress via viral proteins, damaging liver cells and DNA and triggering inflammation and fibrogenesis. Even post-cure, oxidative stress and iron overload may continue to drive disease progression. Genetic and epigenetic factors influence fibrosis progression and HCC risk. Despite a sustained virologic response (SVR), patients with advanced liver damage remain at risk for HCC and metabolic diseases, highlighting the need for continued monitoring and personalized post-treatment care. Full article

Background: Hepatitis B virus (HBV) infection continues to be a major public health concern, especially in sub-Saharan Africa, where widespread epidemics and restricted availability of long-term antiviral therapies result in higher mortality and morbidity rates. Drug repurposing represents a strategic approach to accelerate the discovery of effective therapies by leveraging agents with demonstrated antiviral and immunomodulatory activity. Product Nkabinde (PN) is a patented African polyherbal formulation initially developed for the treatment of HIV. Recent experimental studies demonstrate PN’s potent anti-HIV activity and significant immunomodulatory effects in human immune cells, implicating host-directed mechanisms relevant to chronic viral infections. This study combines an integrative application of network pharmacology and molecular docking to evaluate the repurposing potential of PN as a multi-target agent in HBV. Method: Bioactive components of PN were screened, and compound-associated targets were intersected with HBV-associated genes (proteins) to construct a protein–protein interaction (PPI) network. Topological analysis identified 10 hub targets (STAT1, STAT3, SRC, HCK, EGFR, SYK, PIK3CA, PIK3CB, PIK3R1, and PTPN11). Gene Ontology and KEGG pathway enrichment were performed with an FDR cut-off < 0.05. Significantly enriched pathways included JAK–STAT signaling, chemokine signaling, EGFR-TKI resistance, PI3K complex signaling, and viral infection pathways, particularly those related to Kaposi sarcoma virus and HSV-1, indicating immunoregulatory and antiviral roles. Molecular docking was performed using AutoDock Vina 1.1.2 to evaluate binding affinity and interaction mode of key PN phytochemicals against the hub proteins, and results were compared to their respective co-crystallized ligands. Results: Molecular docking indicated that major phytochemicals from PN exhibited significant binding affinities across all 10 hub host targets, typically outperforming or closely matching their respective co-crystallized ligands. The strongest contacts were observed for β-sitosterol–PIK3CB (−14.2 kcal/mol) and oleanolic acid–SYK (−14.0 kcal/mol), which were significantly stronger than the co-crystallized ligands (−7.9 and −8.3 kcal/mol, respectively), indicating robust stabilization within catalytic and regulatory pockets. Procyanidin B2 toward HCK (−10.5 vs. −7.9 kcal/mol) and PIK3CA (−9.5 vs. −7.3 kcal/mol), quercetin toward PIK3R1 (−10.6 vs. −8.2 kcal/mol) and PTPN11 (−9.2 vs. −7.5 kcal/mol), rutin toward SRC (−10.5 vs. 7.8 kcal/mol), and diosgenin toward EGFR (−9.4 vs. 8.4 kcal/mol). Procyanidin B2 maintained robust multi-hydrogen bonding networks, demonstrating significant binding, despite STAT1 and STAT3 docking showing identical affinities to co-crystals. Conserved hydrogen bonds, π–cation interactions, and significant hydrophobic packing at ATP-binding clefts and regulatory domains supported these interaction patterns, indicating competitive suppression of host signaling nodes taken over by HBV. Conclusions: Together, these results demonstrate that the components of PN possess strong multitarget binding capabilities across the PI3K/AKT, JAK–STAT, SRC-family kinase, EGFR, and SYK pathways, supporting their potential repurposing as host-directed HBV therapeutics with the ability to impede immune evasion, viral persistence, and HBV-associated oncogenic progression. Full article