Search Results (3,799)

The hepatitis B virus (HBV) is a worldwide hepatotropic virus despite the availability of a highly effective vaccine. Currently, the most efficacious treatment against HBV infection is the use of interferon and nucleos(t)ide analogs, which effectively suppress viral replication but do not eradicate infection. Consequently, studies are still ongoing to identify novel molecules with antiviral properties. Interfering with HBV trafficking in infected cells is an approach that would greatly benefit from the diverse techniques of microscopy. However, several challenges arise in employing such techniques for HBV, given the unique characteristics of this virus. Notably, HBV predominantly produces non-infectious subviral particles in addition to infectious virions. Moreover, both virions and SVPs are small objects, measuring only 20 to 40 nm, which challenges their observation using conventional optical microscopy. Additional obstacles include the small size of the HBV genome and its high compaction, which restrict reverse genetics and the introduction of DNA sequences coding for fluorescent polypeptides. In this review, we will provide an overview of ongoing research efforts aimed at visualizing the different stages of the HBV life cycle within infected cells. Furthermore, we will explore solutions successfully applied to the visualization of other viruses that could potentially be adapted to HBV. Full article

Background: Tenofovir alafenamide (TAF) and entecavir (ETV) are recommended alternatives to tenofovir disoproxil fumarate (TDF) for patients with chronic hepatitis B (CHB) at increased risk of kidney injury. However, data from direct head-to-head comparisons of their long-term renal safety and antiviral efficacy after switching from TDF are lacking. We aimed to compare these outcomes between TAF and ETV. Methods: This multicenter retrospective cohort study included consecutive CHB patients who switched from TDF to either TAF or ETV between January 2012 and December 2021. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Changes in estimated glomerular filtration rate (eGFR) were assessed using a linear mixed-effects model. Renal dysfunction was defined as a decline of at least one GFR category. Results: A total of 235 patients were included (TAF, n = 168; ETV, n = 67). After adjustment for key risk factors, the mean eGFR decline over 36 months was not significantly different between the TAF and ETV groups (−3.21 mL/min/1.73 m² [95% CI, −4.98 to −1.44] vs. −3.49 mL/min/1.73 m² [95% CI, −9.49 to −2.50]; p = 0.856). The 3-year cumulative incidence of renal dysfunction was also not significantly different between groups (16.6% [95% CI, 10.5–23.3] vs. 7.8% [95% CI, 2.7–16.2]; p = 0.135). Alanine aminotransferase normalization rates (83.0% vs. 78.8%; p = 0.575) and virological suppression rates (97.8% vs. 97.1%; p = 1.000) were similarly high in both groups. Conclusions: TAF and ETV demonstrated similar long-term renal safety and antiviral efficacy, supporting both agents as reasonable switch options for CHB patients requiring TDF discontinuation because of renal safety concerns. Full article

Background: Elranatamab, a bispecific antibody targeting BCMA and CD3, has demonstrated clinical activity in relapsed/refractory multiple myeloma. Real-world evidence regarding infectious complications and supportive care remains limited. We evaluated the early clinical activity, safety profile, infectious complications, and supportive care practices associated with relapsed/refractory multiple myeloma (RRMM). This study represents one of the first multicenter real-world evaluations of elranatamab in Türkiye. Methods: This multicenter retrospective study included 87 patients with relapsed/refractory multiple myeloma treated with elranatamab. Clinical characteristics, treatment responses, immune-mediated toxicities, infectious complications, and supportive care practices were assessed. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Multivariable analyses were performed to identify factors associated with treatment response and clinical outcomes. Results: At 3 months, ORR was 47.1% in the ITT population, 54.7% in the mITT population, and 83.7% among evaluable patients; corresponding 6-month ORRs were 31.0%, 42.2%, and 81.8%, respectively. The high proportion of patients without landmark response assessments primarily reflected insufficient follow-up, early death, or disease progression. Elevated LDH remained independently associated with lower response probability and inferior clinical outcomes. Cytokine release syndrome (CRS) occurred in 69% of patients, with grade ≥ 3 events in 5.7%, whereas immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent (4.6%) and no grade ≥ 3 events occurred. Grade ≥ 3 infections occurred in 39% of patients, including CMV events requiring antiviral treatment in 24.1%. No HBV reactivation occurred among patients receiving antiviral prophylaxis. Median PFS and OS were 8.1 and 10.6 months, respectively. Conclusions: Elranatamab demonstrated early clinical activity and a manageable safety profile in a heavily pretreated real-world RRMM population. Infectious complications, including CMV events, remained clinically relevant, emphasizing the importance of supportive care. Longer follow-up is needed to characterize long-term outcomes. Full article

Background/Objectives: Interferon-free direct-acting antiviral (DAA) therapy cures chronic hepatitis C virus (HCV) infection, but its short-term effects on health-related quality of life (HRQoL) are captured differently by generic and disease-specific instruments. We examined longitudinal changes in utility scores and HRQoL in a multicenter Japanese cohort. Methods: Adults with chronic HCV completed the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), the 8-Item Short-Form Health Survey (SF-8), and the Chronic Liver Disease Questionnaire (CLDQ) at baseline and at 12, 24, and 36 weeks after treatment initiation; 48-week data were included when available. Complete-case panels were analyzed for each instrument (SF-8, n = 112; CLDQ, n = 131; EQ-5D-5L, n = 128). Domain trajectories were summarized and compared with baseline. Results: By week 36, SF-8 general health improved significantly from 50.42 to 52.47, whereas vitality (50.73 to 52.55) and mental health (51.02 to 53.05) showed nonsignificant numerical increases. CLDQ showed improvements in worry (5.21 to 5.82) and total score (5.21 to 5.47). EQ-5D-5L utility values remained high and largely stable (0.913 to 0.920), suggesting ceiling effects in patients with relatively good baseline health status. External real-world evidence also suggested better on-treatment HRQoL with ribavirin-free regimens. Conclusions: In Japanese patients with HCV, interferon-free DAA therapy was associated with early improvements in symptom-proximal and mental domains of HRQoL. Generic utility scores changed little over the short term, indicating that disease-specific patient-reported outcome (PRO) instruments and utility measures should be used together for patient-centered assessment and cost–utility modeling. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV) is the etiological agent of Kaposi’s Sarcoma (KS), which induces metabolic stress in infected host cells. KSHV reprograms host metabolic pathways for efficient viral replication and infectious virion production. Here, we report a time-course global metabolomics study conducted in iSLK.BAC16 cells to compare latent and lytic KSHV infection. Our data show that amino acid, central carbon, and nucleotide metabolic pathways are highly dysregulated upon reactivation. During lytic KSHV infection, pathway enrichment analysis identifies purine and pyrimidine metabolism as the top two most significantly impacted and dysregulated pathways. Further experiments have shown that nucleotide metabolism is required during lytic KSHV infection to produce maximal infectious virus. Treatment with the FDA-approved drug, methotrexate (MTX), a folate antagonist that decreases nucleotide metabolism by reducing tetrahydrofolate cofactors, significantly reduced KSHV copy number and late lytic viral gene expression upon reactivation compared to controls. Additionally, titers of cell-free supernatants from MTX-treated lytic samples showed a significant reduction in infectious virion production. Furthermore, MTX significantly decreased the viral titer of murine herpesvirus 68 (MHV-68), a model virus to study gammaherpesvirus. Overall, our study demonstrates that metabolic inhibition during lytic gammaherpesvirus infection decreases productive infection and hence serves as a potential therapeutic antiviral target. Full article

Chronic hepatitis B and C are major causes of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. The genetic diversity of hepatitis B virus (HBV) and hepatitis C virus (HCV) influences disease progression, diagnosis, vaccine response, and antiviral treatment. Periods of healthcare disruption, such as the COVID-19 pandemic, reinforce the importance of molecular surveillance to monitor viral genotypes and clinically relevant mutations. This study described the distribution of HBV and HCV genotypes and mutations in Rio de Janeiro, Brazil, during the COVID-19 pandemic. A cross-sectional study included 25 patients (15 HBV and 10 HCV) recruited between 2020 and 2022. Viral nucleic acids were amplified and sequenced by Sanger methodology, and mutations were analyzed using the Geno2pheno platform. HBV genotype A predominated (67%), comprising subgenotypes A1 (40%) and A2 (27%), followed by the rare genotypes B1 (13%), F2 (13%), and G (7%). Among HCV-infected individuals, genotypes 1a (40%) and 1b (30%) predominated, followed by genotypes 4 (20%) and 2 (10%). HBV immune escape mutations (Y100C and T126S) and unusual insertions in the S and RT domains were identified. In HCV, the substitutions C316Y, C316N, and S282R were detected. These findings highlight the importance of molecular surveillance for detecting clinically relevant viral variants. Full article

Background: Geranium robertianum L. (GR) is a perennial herbaceous plant that belongs to the Geraniaceae family, widely distributed across temperate regions of Europe, Asia, North Africa, and America. It has been used in traditional ethnomedicine for its antibacterial, haemostatic, and anti-allergic properties in the treatment of oropharyngeal conditions, wounds, and inflammatory diseases. Beyond these traditional applications, pharmacological studies have documented several biological activities of its extracts and constituents. Objective: The aim of this review is to evaluate the therapeutic potential of GR by examining the phytochemical composition and the pharmacological properties relevant to dental medicine. Methods: A literature screening was conducted (PubMed, Google Scholar, PubMed Central), with focus on studies concerning phytochemical composition, pharmacological effects, and potential applications of GR and its major bioactive constituents in oral health. Results: Phytochemical analysis reveals that GR is characterized by a rich content of polyphenols, particularly tannins, flavonoids, and phenolic acids, with geraniin, ellagic acid, gallic acid, quercetin, and kaempferol identified as its principal bioactive constituents. Recent studies have confirmed that these constituents are responsible for the plant’s therapeutic potential in oral medicine. These compounds possess a variety of effects, from antibacterial and anti-inflammatory properties to antifungal and antiviral activities, as well as antioxidant, wound-healing, and anticancer benefits relevant to dental medicine. Conclusions: Despite its long-standing traditional use, GR remains largely underexplored in the context of oral health. This gap in the literature highlights GR as a promising phytotherapeutic candidate, calling for further in vitro and in vivo studies in order to investigate its efficacy and establish its mechanism of action in dental medicine. Full article

Background and Objectives: Evidence regarding continuation versus withdrawal of immunosuppressive agents during antiviral treatment of cytomegalovirus (CMV) colitis complicating ulcerative colitis (UC) remains limited. We compared molecular remission, clinical outcomes, and relapse according to immunosuppressive-therapy management. Materials and Methods: This prospective, non-randomized, single-center cohort included 44 hospitalized adults with UC and CMV colitis treated with intravenous ganciclovir. Patients were managed according to a clinician-selected strategy of temporary discontinuation (n = 24) or continuation (n = 20) of immunosuppressive therapy. Molecular remission, the primary outcome, was defined as undetectable tissue CMV DNA at day 14. Results: Both groups demonstrated significant clinical and endoscopic improvement. The continuation group had higher residual CMV DNA levels at day 14 (p = 0.003) and more adverse events (p = 0.019). Clinical remission, endoscopic remission, and one-year relapse rates were comparable. Multivariable logistic regression showed that continuation of immunosuppressive therapy was associated with reduced molecular remission (OR 0.26, 95% CI 0.07–0.98; p = 0.045). Corticosteroid exposure was confined to the continuation group (7/20 vs. 0/24), raising the possibility of substantial residual confounding. Conclusions: In this exploratory cohort, clinician-selected continuation of immunosuppressive therapy was associated with a lower likelihood of day-14 molecular remission and more frequent adverse events, without demonstrable additional clinical or endoscopic benefit. However, the observed association may have been influenced by corticosteroid exposure and should not be interpreted as a class-wide effect of immunosuppressive therapy. These hypothesis-generating findings require confirmation in adequately powered multicenter studies before informing routine clinical practice. Full article

Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy. Full article

The 2022–2024 mpox outbreak in Europe was dominated by MPXV Clade IIb and generally mild, but recent Clade I/Ib detections and early local transmission have changed preparedness needs. We performed a PRISMA-ScR scoping review of European mpox evidence from 2022 to 2026, supplemented by global and African data where regional evidence was sparse, covering clades, host determinants of severe disease, and antiviral efficacy and resistance, and ranking the evidence gaps. European Clade IIb surveillance showed very low mortality (10 deaths among 22,662 cases; case fatality 0.04%), contrasting with 3–11% estimates for Clade I/Ib in affected African settings, although comparisons are confounded by age, health-system access and comorbidity. Severe European disease was driven mainly by immune compromise: non-HIV immunosuppression, uncontrolled HIV and CD4 counts < 200 cells/µL were the most consistent markers, while women were a small minority of cases, with higher hospitalisation risk, especially in pregnancy. Tecovirimat failed to improve outcomes in four randomised trials, F13L-associated resistance was reported in advanced HIV, and its European mpox use was subsequently restricted. The evidence base is strongest for mild Clade IIb infection in immunocompetent adults and weakest for the groups most likely to need treatment. Preparedness should prioritise harmonised genomic surveillance, severity-stratified cohort data and adaptive therapeutic trials enrolling immunocompromised, paediatric, pregnant and older patients. Full article

Feline infectious peritonitis virus (FIPV) causes a fatal and immune-mediated disease in cats with limited treatment options. Natural products offer promising antiviral candidates, but animal-derived peptides remain underexplored. Here, we identified PI-8, a Periplaneta americana (P. americana)-derived peptide with validated binding to ISG15, and evaluated its anti-FIPV effect and mechanism. PI-8 showed low cytotoxicity (CC₅₀ > 40 μM) and inhibited FIPV replication with an IC₅₀ of 12.9 μM, acting primarily at the post-entry stage. PI-8 significantly upregulated IFNA1, IFNB, ISG15, and MX1 in infected CRFK cells. In FIPV-infected cats, PI-8 reduced RNA levels in blood, saliva, and anal swabs, and lowered tissue viral burden in liver, spleen, lung, kidney, and intestine. It also alleviated gross and histopathological lesions and decreased inflammatory cytokine expression. These findings suggest that PI-8 is an P. americana-derived peptide with dual anti-FIPV and immunomodulatory activity associated with an IFN-ISG15-related antiviral response. PI-8 represents a potential host-directed therapeutic candidate for FIPV infection. Full article

Background: Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, but their safety in patients with pre-existing hepatitis B virus (HBV) infection remains uncertain. HBV reactivation is a recognized complication of immunosuppressive cancer therapy, yet evidence supporting routine antiviral prophylaxis during ICI treatment is limited. This study evaluated HBV reactivation and HBV-related outcomes among HBV-positive cancer patients receiving ICIs. Methods: This multicenter retrospective cohort study included adult patients treated with ICIs between January 2017 and December 2022. Patients were grouped according to receipt of antiviral prophylaxis. The primary outcome was HBV reactivation during ICI therapy. Secondary outcomes included hepatic flare, severity, and timing of reactivation, response to antiviral therapy, and factors associated with HBV-related outcomes. Results: A total of 160 patients were included; 68 received antiviral prophylaxis and 92 did not. HBV reactivation occurred in 3 patients (1.9%) and the odd ratio between antiviral prophylaxis and HBV reactivation was wide and imprecise (2.76; 95% CI 0.25–31.05). Hepatic flare occurred in 16 patients (10.0%) and was more frequent in the prophylaxis group than in the no-prophylaxis group (19.1% vs. 3.3%; p = 0.001). Conclusion: In this multicenter retrospective cohort study, the HBV reactivation rate was low and could not determine whether antiviral prophylaxis reduced the risk of reactivation. Hepatic flares were significantly more common among patients who received antiviral prophylaxis, likely reflecting a higher baseline risk of HBV-related complications in this group. A future randomized controlled trial is warranted to guide risk-adapted antiviral prophylaxis and monitoring. Full article

This review examines the viral quasispecies concept and its implications for understanding viral evolution, pathogenesis, and the development of effective antiviral therapies. Quasispecies are dynamic populations of closely related but genetically distinct viral genomes, which evolve under mutation and Darwinian selection. Notably, minority variants, often dismissed as “genetic noise”, may harbor significant biological differences—such as drug resistance—and become dominant under changing selective pressures. Next-generation sequencing (NGS) has become an indispensable tool for characterizing genetic diversity within quasispecies, enabling detection and quantitative analysis of minority variants often missed by conventional Sanger sequencing, as well as the calculation of diversity indices. We highlight two NGS-based studies of hepatitis B virus quasispecies as illustrative examples of the relevance of minority variants in antiviral resistance and clinical outcomes. These studies also exemplify transcomplementation, whereby defective viral genomes can be replicated and packaged through functional proteins provided by co-infecting variants. Finally, we discuss how the quasispecies concept may extend beyond viruses, with parallels in biological systems such as the adaptive immune system and tumor cell populations. Recognizing quasispecies as dynamic evolving populations rather than static entities is crucial for developing successful strategies to address infectious diseases and other complex biological challenges. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the global swine industry, partly because current vaccination strategies offer limited protection against heterologous viral strains. Since modified medium-chain fatty acids (mMCFA) offer enhanced structural stability and antimicrobial properties compared with unmodified MCFA, we evaluated a proprietary mMCFA blend (D-Strike, Devenish Nutrition) against PRRSV in vitro and in vivo. In vitro efficacy was assessed using TCID₅₀ assays on MARC-145 cells and a viability qPCR (V-qPCR). At 1:1000, 1:2000, and 1:5000 dilutions, the mMCFA inactivated >4 logs (99.99%) of the virus within 5 min of exposure. The results of V-qPCR were also compatible with those obtained by cell culture assays. For the in vivo study, 40 weaned male piglets were assigned to four dietary treatments: negative control (group A), PRRSV-challenge control (group B), 0.2% D-Strike (group C), and 0.4% D-Strike (group D). Pigs in groups B, C, and D were challenged intranasally with virulent PRRSV. The results demonstrated that dietary mMCFA reduced clinical signs, attenuated a febrile response, and decreased the severity of lung lesions. Some responses appeared more pronounced at the 0.4% inclusion level than at 0.2%, although a formal dose–response analysis was not statistically significant for most outcome measures. The sera from the 0.4% D-Strike group showed 65% lower PRRSV than the positive control, although this difference was not statistically significant. In addition, this group had 0% mortality as compared to 20% in the positive control group. Feed efficiency also improved in D-Strike-fed pigs. These findings indicate that mMCFA shows promise as a feed additive for mitigating PRRSV infection, although the in vivo antiviral effects require confirmation in larger studies. Full article

Background/Objectives: Acute respiratory infections represent a global health burden due to their high incidence, morbidity and mortality. Despite advances in prevention and treatment, strategies providing broad protection against respiratory pathogens remain limited. This study evaluated the antiviral activity of nasal spray forms based on an antigen complex from opportunistic bacteria, with or without a mucoadhesive copolymer, and their influence on cellular and humoral components of the immune response. Methods: Antiviral activity was assessed in experimental models of SARS-CoV-2 infection in Syrian hamsters and influenza A pneumonia in mice under prophylactic and therapeutic–prophylactic regimens. Parameters of cellular and humoral immune response were assessed using delayed-type hypersensitivity, antibody-forming cell assays, and leukocyte phagocytic activity. Results: Both forms showed comparable influence on cellular and humoral components of the immune response. In a mouse model of lethal influenza pneumonia induced by A/California/04/2009 (H1N1)pdm09 virus, intranasal administration at 100 µg/kg increased mean survival time and survival rate, and reduced body weight loss. In SARS-CoV-2-infected hamsters, both forms reduced clinical signs, body weight loss, weight lung index, lung pathology, and decreased viral titers. The copolymer-containing form showed the most pronounced effect under the therapeutic–prophylactic regimen, with greater protection against body weight loss and stronger suppression of viral replication. Conclusions: The findings support further investigation of these nasal spray forms as candidates for prophylaxis and adjunctive therapy of respiratory infections, particularly when pathogen variability may limit the effectiveness of pathogen-directed treatments. Further mechanistic studies are needed to clarify the pathways underlying the observed antiviral effect. Full article