Search Results (5,200)

Belatacept, a selective costimulation blocker targeting the CD28–CD80/86 pathway, represents a major innovation in solid organ transplantation immunosuppression. By providing upstream inhibition of T-cell activation without calcineurin inhibition, belatacept offers the potential for improved long-term graft and patient outcomes with reduced nephrotoxicity and metabolic adverse effects. This review summarizes the mechanistic rationale, pivotal evidence, and clinical experience supporting the use of belatacept as first-line or conversion therapy in solid organ transplantation, while addressing safety, pharmacoeconomic impact, and future research directions. A comprehensive analysis of pivotal phase II–III trials (BENEFIT, BENEFIT-EXT), recent prospective conversion studies, and ongoing trials in liver, heart, and lung transplantation was performed. Safety data and health–economic evaluations were critically appraised. In kidney transplantation, belatacept-based immunosuppression provides superior renal function and improved metabolic profiles compared with calcineurin inhibitors (CNIs), though with higher early acute rejection rates. In liver, heart, and lung transplantation, evidence remains limited, with de novo use contraindicated in liver grafts due to excess mortality and rejection. Conversion from CNI to belatacept in selected patients improves renal outcomes without compromising graft survival. Safety considerations include a higher risk of post-transplant lymphoproliferative disorder (PTLD) in Epstein–Barr virus-negative recipients. Belatacept represents a paradigm shift in transplant immunology by targeting upstream T-cell activation. While currently approved only for kidney transplantation, ongoing studies in thoracic and hepatic grafts may expand its therapeutic role. Personalized patient selection, combination regimens mitigating rejection risk, and real-world cost-effectiveness analyses will define its place in future precision immunosuppression strategies. Full article

Cuba is in a unique situation in which it has a large (220,000 managed colonies) and isolated honey bee population due to a 60+ year ban on the importation of bees. Despite this, the ectoparasitic mite Varroa destructor arrived in 1996, and with it came deformed wing virus (DWV). In 2018, an island-wide survey detected varroa and DWV in 91% of colonies. In this study, we conducted a full-virome analysis on some of these samples, along with additional samples collected in 2021. For the first time, we detected two variants of Lake Sinai Virus and confirmed the absence of the normally widespread black queen cell virus in Cuba. We also detected both DWV-A and DWV-B master variants, with DWV-B being the dominant variant. Interestingly, the DWV-B/A recombinant was also detected, indicating that despite Cuba’s isolated nature, the pattern of DWV evolution mirrors that found in the USA and Europe. However, this pattern is not found in neighboring Latin America, China, or Japan, where the DWV-A master variant continues to be dominant. How and why two distinct evolutionary DWV pathways have arisen remain a mystery. Full article

The first major HIV outbreak in the Eastern Europe and Central Asia (EECA) region was registered. Phylogeographic analysis revealed that the main exporters of the virus were Donetsk and Lugansk, from which most migration events occurred, and the predominant genetic variant in Donetsk was subtype A. However, despite a relatively high level of understanding of HIV genetic diversity, data on resistance mutations remain limited. The aim of this study is to assess HIV genetic diversity and drug resistance in Donetsk, Luhansk and Zaporizhzhia regions. A comprehensive examination was conducted, encompassing 392 sequences covering the integrase-coding region of the HIV-1 pol gene. Subtyping was achieved through various programs, including COMET, the Stanford Database, BLAST and REGA. The study also involved phylogenetic analysis to clarify HIV genovariants. The profiles and levels of drug resistance were determined. The overall prevalence of drug resistance mutations to the integrase strand transfer inhibitors (INSTIs) among the studied patients was 3.6% (95% CI, 1.7–5.4%). The most commonly detected major DRMs for INSTIs were G140R (4, 28.6%) and Y143R (3, 21.4%), followed by R263K (2, 14.3%), G140RG (2, 14.3%), Y143YS (2, 14.3%), Y143YC (1, 7.1%) and Q148QR (1, 7.1%). A high-level resistance was observed for RAL—8/14 (57.1%), CAB—6/14 (42.9%) and EVG—2/14 (14.3%). The results presented are part of a further larger study and are preliminary. The results of this study suggest a moderate HIV-1 resistance situation in the Donetsk, Luhansk and Zaporizhzhia regions, but require further monitoring. Full article

Plant viruses cause substantial yield and quality losses worldwide, and their rapid evolution can erode deployed host resistance. This review synthesizes current knowledge of antiviral resistance and tolerance mechanisms, using barley yellow dwarf virus (BYDV) in cereals as an illustrative case study. We first summarize key layers of plant antiviral immunity, including pre-formed physical and chemical barriers, dominant and recessive resistance genes, RNA silencing, hormone-regulated defense signaling, and degradation pathways such as the ubiquitin–proteasome system and selective autophagy. We then discuss how these mechanisms are exploited in breeding and biotechnology, covering conventional introgression, marker-assisted selection, QTL mapping and pyramiding, induced variation (mutation breeding and TILLING/ecoTILLING), transgenic strategies (pathogen-derived resistance and plantibodies), RNA interference-based approaches, and CRISPR-enabled editing of susceptibility factors. Finally, we highlight emerging nano-enabled tools and propose integrated strategies that combine genetic resistance with surveillance and vector management to improve durability under climate change and ongoing viral diversification. Full article

Citrus yellow vein clearing virus (CYVCV) is the causative agent of the yellow vein clearing disease (YVCD), a worldwide and highly destructive disease in lemon (Citrus lemon) and sour orange trees (C. aurantium). The typical symptoms of vein clearing are believed to be associated with CYVCV infection in citrus, so virus-specific diagnostic systems are currently used to confirm infection. In the present study, virome analysis based on high-throughput sequencing (HTS) on a lemon plant showing YVCD revealed mixed infection of CYVCV, iris domestica betaflexyviridae 1 (IDBV), and hop stunt viroid (HSVd). This multiple infection was confirmed in other two lemon plants with similar symptoms using virus/viroid specific primers. This is the first report of IDBV in lemon. Through molecular characterization and the reconstruction of phylogenetic relationships, a possible origin of the viruses/viroid identified in lemon has been hypothesized. Such mixed infections raise new questions about their role in the expression of YVCD symptoms observed on lemon. Full article

The family Arenaviridae encompasses zoonotic, rodent-borne pathogens (e.g., Lassa, Machupo, and Junín viruses) that cause severe viral hemorrhagic fevers with high case fatality rates. The current therapeutic landscape is severely limited, underscoring the urgent need for novel antiviral strategies. A promising approach involves combining directly acting antivirals with host-targeted antivirals. A compelling host-targeted antiviral target is the aryl hydrocarbon receptor (AHR). This ubiquitous ligand-activated transcription factor is a recognized pro-viral host factor across multiple viral families. Building on prior work with Junín and Tacaribe viruses, we investigated whether the AHR inhibitor CH223191 could enhance the virus-directed antiviral activity of favipiravir against these viruses. First, we evaluated the toxicity and antiviral potential of CH223191 against a lethal Junín virus infection in male and female hTfR1 mice. After demonstrating substantial protection, we conducted preliminary assays to study the antiviral effects of combining CH223191 and favipiravir on Tacaribe virus (TCRV) infections in the Vero cell culture model. We observed synergistic interaction with all four models (ZIP, Loewe, Bliss, and HSA). We next determined the sub-optimal dose of favipiravir and conducted an antiviral combination study in the male and female AG129 mouse model infected with TCRV. The combination effectively protected mice from a lethal TCRV infection and showed cooperative effects, reducing weight loss and viral loads. Overall, these results show that the AHR is a promising pharmacological target for the development of novel antivirals. Furthermore, we discovered a cooperative interaction between the activities of favipiravir and CH223191. Full article

Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus–host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology. Full article

Background/Objectives: While new vaccines are in development; one strategy to increase influenza vaccine coverage is to repurpose current influenza vaccines for intranasal delivery. Methods: To address this goal; mice were vaccinated intranasally with either a split inactivated virus vaccine (Fluzone) or a recombinant HA vaccine (Flublok) at one of two doses (1 μg high dose or 0.1 μg low dose). Both vaccines were adjuvanted with either a STING agonist; c-di-AMP (CDA); or a combination of a synthetic toll-like receptor (TLR) 4 and TLR7/8 agonist (TRAC478). Results: Mice vaccinated with either vaccine plus adjuvant had higher hemagglutination-inhibition titers than mice administered unadjuvanted vaccines. Mice vaccinated with either vaccine plus CDA had on average higher numbers of H3 and influenza B hemagglutinin (HA)-specific antibody-secreting cells (ASCs); whereas mice vaccinated with vaccine plus TRAC478 had on average higher number of H1 HA-specific ASCs. All vaccinated mice challenged with the H1N1 influenza virus were protected against both morbidity and mortality with no detectable virus in their lungs. Mice challenged with the H3N2 influenza virus all lost weight over the first 5 days of infection. Adding TRAC478 with either a high or low dose vaccine resulted in 80–100% survival following challenge. Almost all mice vaccinated with Flublok plus CDA died from H3N2 influenza virus challenged with ~2 logs higher viral lung titers than mice administered Flublok only or Flublok plus TRAC478. Conclusions: Overall; Fluzone and Flublok can effectively be used for intranasal vaccination. Full article

In recent years, numerous researchers have investigated various preventive strategies against respiratory viruses that pose a threat to human health. This study aims to develop a nasal spray formulation based on the natural polysaccharide xanthan gum (XG) and camostat, and to evaluate its dual protective mechanism at the nasal mucosa, the primary entry point for respiratory viral infections. The efficacy of the formulation was assessed through physicochemical characterization, cell-based assays, and animal experiments. Initially, muco-adhesiveness was evaluated by monitoring the drying dispersion area of the test formulation over time on a Petri dish. The combination of XG and camostat exhibited a dispersion area more than ten times larger than that of each component used alone. The antiviral efficacy was demonstrated in both human nasal epithelial cells (HNEc) and an influenza-infected mouse model. The cell-based experiment demonstrated a significant inhibition of viral penetration and replication. Furthermore, suppression of transmembrane protease, serine 2 (TMPRSS2) expression, a key factor in influenza virus entry, was observed in mouse lung tissues. These findings suggest that the Camostat–Polysaccharide Dual-Action Nasal Spray (CPNS), currently under development, holds promise as a non-invasive, first-line barrier to prevent the initial infection and replication of respiratory viruses. Full article

Guanidinoacetate methyltransferase (GAMT) is an essential enzyme in the biosynthesis of creatine, an important molecule in energy recycling. GAMT loss of function leads to GAMT deficiency (GAMT-D), an autosomal recessive disorder resulting in low creatine levels and the accumulation of a toxic intermediate, guanidinoacetate (GAA). GAMT-D patients present with intellectual disability and epilepsy, emphasizing the detrimental consequences of disturbed creatine metabolisms in the central nervous system (CNS). Current treatments are not curative and may not restore creatine metabolism in the brain. Here, we present a proof-of concept study testing the first CNS-directed, Adeno-associated virus serotype 9 (AAV9)-based gene therapy for the treatment of GAMT-D. the delivery of GAMT construct to cellular models of GAMT-D effectively restored protein and mRNA expression of GAMT while increasing intracellular creatine content and decreasing GAA accumulation. In murine models of GAMT-D, treatment with scAAV9.hGAMT, delivered intrathecally, resulted in increased creatine content as well as significant decreases in GAA accumulation in the CNS and peripheral organs. Overall, we found that scAAV9.hGAMT represents a promising gene therapy for treating GAMT-D, warranting further investigation in animal models to determine an appropriate therapeutic window for both efficacy and safety that allows for translation into human patients in the future. Full article

Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on RSV epidemiology and genotypic distribution across the FSU. Published studies from eLIBRARY and PubMed databases queried for RSV prevalence data, together with public health surveillance datasets, were used to summarize RSV prevalence research across eight FSU countries. Random-effects meta-analysis across age strata showed high prevalence in children before 6 (21%) and a progressive decline with age, which is in agreement with global data. Prevalence estimates showed a high degree of variability partially explained by study scope and clinical presentation. We observed COVID-19-related seasonal disruptions of RSV seasonality, followed by gradual post-pandemic stabilization. Genotypic data reflects global trends with two cosmopolitan clades, A.D and B.D, and their descendants, dominating in the region. The review is limited by uneven geographical and temporal coverage, and scarce data on adults. The review provides the first integrated summary of RSV epidemiology across the FSU and underscores the need for expanded regional surveillance and genomic reporting. Full article

Background & Aims: Hepatitis C virus (HCV) infection remains one of the most significant and lethal infectious diseases worldwide. Since the approval of the first direct-acting antiviral agent in 2013, the therapeutic landscape has changed dramatically, with SVR rates exceeding 95%. The WHO set the ambitious goal of achieving global HCV elimination in 2030. High-risk populations remain among the most challenging yet essential groups to treat in order to reach this objective. The aim of this study is to describe two distinct approaches targeting high-risk populations to advance HCV elimination. Methods: An observational study was conducted from April 2017 to August 2025, including patients evaluated and treated at Porto’s correctional facility and Porto’s addiction centers. All patients received DAA therapy, and the primary outcome was sustained virological response at 12 weeks post-treatment. Results: A total of 124 patients from the prison setting were included. Their mean age was 43.0 ± 8.4 years, and all were males. Treatment with DAA resulted in an SVR of 99.2%. In addition, 43 patients from the addiction centers were included, with a mean age of 54.9 ± 5.9 years, and the majority were males (86%). These patients achieved an SVR 12 of 97.7%. Conclusions: In two distinct and difficult-to-reach high-risk populations, we demonstrated that a tailored approach involving on-site evaluation and treatment of HCV infection is highly effective and may be crucial to achieving HCV elimination. Full article

Background/Objectives: Infections remain a leading cause of morbidity and mortality following liver transplantation, with bloodstream infections (BSIs) representing one of the most critical complications. This study aimed to identify factors associated with mortality in liver transplant recipients who developed BSIs over a 10-year period. Methods: This retrospective study was conducted at a tertiary university hospital between 1 April 2014 and 31 December 2024. A total of 467 adult patients underwent liver transplantation during the study period. Among 467 patients, a total of 210 bloodstream infection episodes occurring in 136 patients were included in the study. Results: BSIs occurred in 29.1% (136/467) of patients, with a total of 210 episodes. The median age was 55 years (IQR: 45–63). Most transplants (95.2%) were from living donors. Hepatitis B virus infection (27.1%) was the most common underlying etiology of cirrhosis. The majority of BSIs (61.2%) occurred within the first three months post-transplant. A total of 242 pathogens were isolated, with ESBL-producing Enterobacterales identified in 72.6% and carbapenem-resistant Enterobacterales (CRE) in 30.1% of cases. Notably, carbapenem resistance among Klebsiella spp. was high at 51.78%. The overall mortality rate was 14.28%. Multivariate analysis identified that a high Pitt Bacteremia Score (hazard ratio [HR] 1.502, 95% confidence interval [CI] 1.361–1.657, p < 0.001) and CRE infection (HR 3.644, 95% CI 1.380–9.620, p = 0.009) were independent predictors of mortality. Conclusions: BSIs are a significant post-transplant complication with high antimicrobial resistance. The Pitt bacteremia score is a strong predictor of mortality and may guide early risk stratification and clinical management in liver transplant recipients. Full article

Recognizing cervical cancer as a major public health concern, Romania was among the first EU countries to introduce human papilloma virus (HPV) vaccination in 2008. Despite multiple strategies implemented over the past 17 years, HPV vaccine coverage remains one of the lowest in the EU, while cervical cancer mortality rates are among the highest. To explore the underlying factors, we conducted a cross-sectional study involving 209 family physicians at the national level. The study assessed their attitudes, practice, knowledge, and training needs related to HPV vaccination. The majority of physicians (90%) reported that they provide HPV vaccination services, and 88.5% considered themselves to have good and very good knowledge about HPV, which they routinely share during consultations with patients. However, respondents noted that both physician and public attitudes toward HPV vaccination are only moderately positive, which limits vaccine uptake and the success of prevention efforts. Parental hesitation was the main barrier, mentioned by 81.8% of respondents. The majority (71.3%) of doctors indicated that they were able to adequately respond to patients’ questions, but 81.4% of respondents expressed the view that additional training is needed for healthcare professionals on HPV infection and vaccination. These findings highlight the need for coordinated efforts to increase demand and trust in HPV vaccination. Recommended strategies include targeted professional training, public information campaigns, and the development of strong cross-sector partnerships to support vaccination efforts. Full article

Paper-based rapid tests are widely used in point-of-care diagnostics due to their simplicity and low cost. However, their application in quantitative analysis remains limited. In this work, a nucleic acid lateral flow assay (NALFA) was integrated with an automated image acquisition system built on a Raspberry Pi platform for the quantitative detection of SARS-CoV-2 virus, increasing the accuracy of the test compared to subjective visual interpretation. The assay employed blue polystyrene microspheres as reporters, while automated image capturing, image processing and quantification were performed using custom Python software (version 3.12). Signal quantification was achieved by comparing the grayscale intensity of the test line with that of a simultaneously captured negative control strip, allowing correction for illumination and background variability. Calibration curves were used for the training of the algorithm. The system was applied for the analysis of a series of samples with varying DNA concentrations, yielding recoveries between 84 and 108%. The proposed approach integrates a simple biosensor with an accessible computational platform to achieve full low-cost automation. This work introduces the first Raspberry Pi-driven image processing approach for accurate quantification of NALFAs and establishes a foundation for future low-cost, portable diagnostic systems targeting diverse nucleic acids, proteins, and biomarkers. Full article