Search Results (1,037)

Hepatitis B virus (HBV) infection remains a major public-health challenge in Peru, particularly in historically hyperendemic Amazonian and Andean regions; however, the structure, evolution, and equity of national HBV research have not been systematically evaluated. We conducted a PRISMA-informed bibliometric analysis of all peer-reviewed and theses on HBV in Peru published between 1988 and 2023 using Scopus, Google Scholar, and the Peruvian National Repository (RENATI). Bibliometric indicators, collaboration networks, thematic structure, and temporal thematic evolution were analyzed in R using bibliometrix- and network-based approaches. The final corpus comprised 232 documents, with a marked increase in production after 2005 and a publication peak in 2018. Scientific output was strongly concentrated in Lima-based institutions, while several departments historically associated with HBV endemicity exhibited minimal or absent research production. Nearly half of the corpus corresponded to undergraduate and postgraduate theses. Thematic analyses revealed persistent predominance of epidemiology, seroprevalence, and vaccination-related research, whereas molecular virology, therapeutics, and translational research remained peripheral or poorly represented. International collaboration was markedly limited. Overall, Peruvian HBV research has expanded quantitatively but remains geographically centralized and shows only limited correspondence with the contemporary geographic distribution of HBV incidence, while also remaining only partially aligned with the contemporary global HBV research frontier. These findings provide an evidence-based framework to guide research-priority setting, territorial equity policies, and strategic investment in infectious disease research capacity in Peru. Moreover, the weak association observed between scientific production and departmental HBV incidence suggests that factors beyond contemporary epidemiological burden contribute to the current distribution of research activity in Peru, highlighting a critical but often overlooked dimension of health inequity in low- and middle-income countries (LMIC) research systems. Full article

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus–host interactions, especially protein–protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction. Full article

The concurrent circulation of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unveiled complex host–pathogen interactions governed by temporal dynamics of innate immune activation. This narrative review synthesizes evidence from human air–liquid interface (ALI) epithelial models, animal studies (hamster, ferret), clinical cohorts, and randomized controlled trials (2015–2026) to delineate the molecular mechanisms underlying viral interference between these two major respiratory pathogens. Prior IAV infection induces a robust type I/III interferon (IFN) response and broad interferon-stimulated gene (ISG) upregulation that restricts subsequent SARS-CoV-2 replication within a critical 24–72 h temporal window. Conversely, SARS-CoV-2 employs a multi-layered immune evasion strategy that blunts IFN induction, providing minimal heterologous protection. Simultaneous co-infection tends to exacerbate disease severity. Host genetic determinants, including OAS1 and TLR7 variants, modulate interference capacity. Therapeutically, early pegylated IFN-λ shows clinical benefit, while experimental evidence from in vitro and animal models suggests oseltamivir may paradoxically reduce IAV-induced interference. These findings underscore the need for multi-pathogen diagnostics, temporally informed clinical decision-making, and IFN-based therapeutic strategies during co-circulation periods. Full article

Outbreaks of avian infectious bronchitis virus (IBV) often occur in vaccinated flocks. The antibody-dependent enhancement (ADE) has been proposed as a potential mechanism underlying coronavirus vaccine failure. However, this hypothesis has yet to be substantiated in flocks. This study demonstrates ADE occurrence in IBV (gamacoronavirus) in vitro and in vivo. Using the SPF chicken host model, primary infection with an O-glycosylation-modified attenuated strain enhanced pathogenesis upon secondary homologous/heterologous virulent challenge, increasing morbidity/mortality (≥30%), pathological lesions, and viral loads. Notably, sequentially attenuated infections also induced ADE, suggesting live attenuated vaccine risks. The immune serum raised against the O-glycosylation-modified attenuated strain was also pre-mixed with the challenge strain, and the mixtures were then inoculated into target cells, non-susceptible macrophage cells, or a co-culture of both cell types. The serum-virus complexes replicated poorly in macrophages, yet immune cells amplified the expression of inflammatory factors and ADE-mediated viral replication in target cells, indicating a significant promoting role of immune cells in this process. The concentrations of complement component C3 and neutralizing antibodies in the immune serum were also measured, and results showed that the induction of this ADE is associated with high complement component C3 and low neutralizing antibody titers. These findings highlight risks for vaccines and antibody-based therapeutic strategies of coronavirus infection. Full article

Emerging viral diseases continue to pose major challenges to global health, creating demand for materials that can support pathogen control, diagnosis, and therapy. Owing to their tunable structures and versatile biointerfaces, metal–organic frameworks (MOFs) have attracted increasing attention in anti-pathogen applications. While previous studies have often focused on individual functions such as catalysis, biosensing, or drug delivery, a broader perspective on the functional development of MOF-based systems remains limited. In this Review, we summarize recent advances in MOF-enabled pathogen inactivation, diagnostic biosensing, host-directed intervention, and virus-inspired therapeutic platforms. Emerging opportunities in antiviral drug discovery and artificial intelligence-assisted materials design are also discussed. In addition, key challenges associated with structural stability, biosafety, scalable fabrication, and clinical translation are highlighted. This Review provides an overview of current progress and outlines perspectives for the future development of MOF-based anti-pathogen technologies. Full article

Background: Scalability and cost remain major manufacturing barriers limiting broad patient access to adeno-associated virus (AAV) gene therapies. While capsid engineering has advanced vector biology, comparatively fewer innovations have addressed fundamental upstream productivity constraints. Transient triple-plasmid transfection is still the dominant AAV production platform and relies on large bacterial backbone plasmids that impose DNA burden and contribute significantly to the cost-of-goods. Methods: In this study, we evaluated a compact Nanoplasmid^TM DNA system (Aldevron) as a structural redesign of the transfection substrate to enhance upstream productivity. Conventional pUC-based triple-plasmid systems were compared to fully substituted Nanoplasmid^TM equivalents across suspension HEK293 production platforms optimised via response surface Design of Experiments. Hybrid plasmid configurations were also constructed to assess component-level contributions. Results: Complete substitution with Nanoplasmid^TM resulted in up to a 10-fold increase in vector genome titre relative to conventional plasmids under matched conditions. Hybrid systems failed to recapitulate this improvement, demonstrating that full-system backbone minimisation is required to ensure high yield. Productivity gains were preserved across transfection reagents and suspension media. Nanoplasmid^TM deployment represents a scalable, capsid-independent upstream intensification approach that improves yield without altering capsid biology. Conclusions: Integration of this approach within a design-for-manufacturability framework offers a practical route to reducing bacterial plasmid elements increasing safety, enhancing process robustness, and improving economic feasibility of AAV therapeutics. Full article

The recurrent emergence of viral outbreaks, including SARS-CoV-2, influenza, Ebola, and respiratory syncytial virus (RSV), continues to expose critical limitations in conventional antiviral therapies, particularly in terms of targeting specificity, bioavailability, and resistance development. Nanotechnology has emerged as a transformative approach to overcome these challenges. This review provides a comprehensive and critical analysis of nanoparticle-based antiviral systems, including lipid-based, polymeric, inorganic, and hybrid nanocarriers, with a focus on their roles in enhancing drug delivery, targeting precision, and therapeutic efficacy. These platforms exert antiviral effects through multiple coordinated mechanisms, including inhibition of viral entry, suppression of replication, gene silencing, and modulation of host immune responses. The clinical success of lipid nanoparticle-based mRNA vaccines highlights the translational potential of nanotechnology, while emerging nanotherapeutic strategies demonstrate increasing versatility across diverse viral pathogens. However, key challenges—including safety, scalability, formulation stability, and regulatory constraints—continue to limit widespread clinical implementation. Overall, nanoparticle-mediated antiviral systems represent a multifunctional and adaptable platform capable of addressing the limitations of conventional therapies and enabling more effective, resilient, and precision-driven strategies for future pandemic preparedness. Full article

African swine fever (ASF) is an acute, febrile, and lethal pig disease induced by the African swine fever virus (ASFV). In the absence of an effective vaccine, early diagnosis is essential for the prevention and control of ASF disease. The p54 protein is important for ASFV diagnosis and vaccine design. In this study, ASFV p54 protein was constructed, expressed, purified, and used to generate three mAbs, namely 9A3, 5H2, and 2G6. Epitope mapping was performed using alanine mutants; the minimal linear epitope recognized by 9A3 and 5H2 was ⁵⁶KKKAAAI⁶², and the minimal linear epitope recognized by 2G6 was ¹⁰⁸TNRPATN¹¹⁴. Of these, ⁵⁶KKKAAAI⁶² was identified as a new linear epitope for the first time. The epitopes were highly conserved in at least genotypes I and II. Alanine-scanning mutagenesis further revealed that residues 56K, 57K, 60A, 61A, 62L, 108T, 110R, 111P, 113T, and 114N were the core sites involved in antibody recognition. Overall, the mAbs and epitopes of the p54 protein identified in this study provide theoretical support for the development of ASFV vaccines based on the B cell epitope, the development of ASFV therapeutic antibody drugs, and the development of ASFV diagnostic tools. Full article

The molecular mechanisms governing the efficient packaging of the large SARS-CoV-2 RNA genome into progeny virions remain incompletely understood, with the role of untranslated regions (UTRs) being particularly enigmatic. Leveraging proximity ligation sequencing data, we identified direct, high-frequency interactions between the viral packaging signal PS9 and both the 5′ and 3′ UTRs during intracellular replication stages. Functional validation using an infectious virus-like particle (iVLP) system demonstrated that genomes incorporating SARS-CoV-2 UTRs exhibited significantly enhanced packaging efficiency, yielding an increase in both packaged RNA copies and reporter gene expression post-infection. Competitive packaging assays confirmed the UTRs confer a selective advantage during particle assembly. Mechanistically, Western blot and digital Western analysis revealed that UTR-containing iVLPs incorporated approximately 2-fold more nucleocapsid (N) proteins, suggesting enhanced N recruitment or retention. The deletion of specific core sequences within the UTRs predicted to form a base pair with PS9 abrogated this enhancement, suggesting the functional significance of the UTR-PS9 interaction interface. Collectively, these results establish that the 5′ and 3′ UTRs act synergistically through direct RNA-RNA interactions with PS9 to promote N protein recruitment and enhance packaging efficiency in a PS9-dependent iVLPs system. This UTR-PS9 regulatory axis presents a novel target for therapeutic intervention against SARS-CoV-2 and related coronaviruses. Full article

Background: Viral vectors are indispensable tools in gene therapy and neural circuit mapping, offering promising therapeutic strategies for diverse genetic diseases and advancing neuroscience research. To achieve high transduction efficiency while mitigating impurity-induced immunogenicity, the development of viral vectors with improved purity and quality is essential. However, this critical requirement is often unmet by conventional purification methods such as ultracentrifugation, which are time-consuming and frequently result in limited product purity. The pseudorabies virus (PRV) is extensively employed as a viral tool for mapping neural circuits, where improved purity contributes to enhanced accuracy of neural tracing. PRV531 is a retrograde trans-synaptic tracer modified from the PRV Bartha strain, specifically designed to facilitate the precise visualization of hierarchical neural networks. Methods: In this study, we developed a method for the concentration and purification of PRV531 by integrating hollow fiber ultrafiltration (HF) with Capto^TM Core 700 (CC700) chromatography. Initially, to concentrate the viral supernatant, a 500 kDa HF membrane was employed, maintaining a feed flow rate of 80 mL/min, a shear rate ranging from 2000 to 6000 s⁻¹, and a transmembrane pressure (TMP) between 0.5 and 1 bar. Following concentration, the virus underwent purification through CC700 chromatography, operating at linear flow rates ranging from 100 to 300 cm/h. Results: Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) revealed distinct bands consistent with the expected sizes of major PRV structural proteins, each with molecular weights ranging from 25 kDa to 150 kDa, concurrently demonstrating a substantial reduction in host cell proteins (HCPs) contamination. The purified PRV531 achieved a high final infectious titer of 3.55 × 10⁹ PFU/mL, with an overall functional virus recovery of 8.88% from the crude supernatant to the final product. Conclusion: These data demonstrate that TFF combined with CC700 resin can efficiently purify retrograde trans-synaptic PRV tracer. Furthermore, this approach provides a promising strategy for purifying other viral-based tracers that traditionally rely on conventional centrifugation methods. Full article

Monitoring immunosuppression in kidney transplant recipients remains challenging, as conventional therapeutic drug monitoring (TDM) reflects pharmacokinetic exposure rather than the overall functional immune state. Torque teno virus (TTV), a non-pathogenic virus, has emerged as a potential complementary biomarker of the net state of immunosuppression. This review evaluates the current evidence regarding the utility of TTV load in this context, focusing on its correlation with standard pharmacokinetic markers, the analytical performance of quantitative PCR assays, its role as an integrated marker of immunosuppression, and its predictive value for clinical outcomes. Available data indicate that TTV load shows weak and inconsistent correlations with individual drug levels, such as tacrolimus trough concentrations, supporting its role as a complementary rather than substitutive tool. qPCR-based assays demonstrate generally good sensitivity and reproducibility, although inter-assay variability and lack of standardization remain important limitations. Clinically, higher TTV levels have been associated with an increased risk of opportunistic infections, whereas lower levels have been linked to acute rejection, suggesting a potential association between TTV viremia and immune status. TTV monitoring may represent a promising complementary approach for a more individualized assessment of immunosuppression. However, further prospective and interventional studies are required to validate standardized thresholds and determine whether TTV-guided strategies improve transplant outcomes compared with conventional monitoring. Full article

Extensive efforts have been undertaken by numerous researchers to control respiratory viruses across the domains of diagnosis, prevention, and treatment. In this study, we developed a niclosamide–polysaccharide nasal spray (NPNS) formulation based on xanthan gum (XG), a naturally derived polysaccharide, and niclosamide, a conventional anthelmintic agent. We then evaluated its therapeutic efficacy following intranasal administration under influenza virus-infected conditions. NPNS was assessed for cytotoxicity under Good Laboratory Practice (GLP) conditions in accordance with ISO 10993-5, and no cytotoxic effects were observed. In influenza virus-infected human nasal epithelial cells (HNEc), NPNS treatment resulted in at least 92.5% suppression of viral gene expression. Furthermore, NPNS demonstrated significantly greater antiviral activity compared to Placebo 1 and Placebo 2, which were formulated by excluding niclosamide and XG, respectively. Owing to the physicochemical properties conferred by XG, NPNS exhibited prolonged retention on the nasal mucosa in a mouse model. Consistently, NPNS showed potent antiviral efficacy in influenza-infected mice. In addition, NPNS treatment was associated with the downregulation of S-phase kinase-associated protein 2 (SKP2), a host factor known to facilitate intracellular viral replication. Collectively, these findings suggest that NPNS may serve as a first-line protective barrier during the early stage of influenza infection by simultaneously blocking viral entry and suppressing viral replication through its dual physicochemical and molecular mechanisms. Full article

Herpesvirus infections belong to major pathogens in the human population. This study aimed at evaluating diagnostic data for eight human herpesviruses, based on datasets derived from a large European tertiary care center. Specifically, we analyzed 118,692 herpesvirus submittals to the Diagnostic Division of the Virological Institute, University Hospital Erlangen (UKER), Germany, between July 2014 and June 2024. Our points of focus were the following: (i) the frequencies of herpesvirus diagnostic results with positivity rates, (ii) departments representing main sample submitters, (iii) the specific importance of intensive care units (ICUs), (iv) the COVID-19 pandemic period, and (v) distinct properties of sample types. Overall, we are stating the highest frequencies of diagnostic assessment for herpes simplex virus (HSV), human cytomegalovirus (HCMV), and Epstein–Barr virus (EBV) infections, pointing to their dominant relevance for clinical practice. Notably, HCMV submittals (46.6% of total), together with EBV (26.2%) and HSV (15.7), accounted for almost 90% of all herpesviral diagnostic samples during this period. Within these key groups, HCMV, EBV and HSV showed positivity rates of 14.5%, 35.0%, and 18.5%, respectively. Concerning a main input of sample submittals, two departments were predominant in our center, i.e., the Departments of Haematology–Oncology and Anaesthesiology. These included patients under multifold types of treatment associated with an increased risk of herpesvirus reactivation or primary infection. Furthermore, another high portion of submittals was noted for ICUs and external sources. In addition, a numerical, transient increase in herpesvirus diagnostic submittals, from various sources, was shown for the COVID-19 pandemic years (mostly 2021) as compared to other periods. Combined, these data underlined the importance of clinical monitoring of herpesvirus infections, particularly for high-risk patients, and the steady need of improvements in preventive measures, therapeutic options, and safe diagnostic tools. Full article

Background/Objectives: As important post-transcriptional and epigenetic regulators of gene expression, miRNAs play a pivotal role in modulating host–virus interactions. While prior reviews have addressed either direct miRNA–HIV genome interactions or miRNA-mediated immune modulation in isolation, the integrated dual functionality of these molecules has not been systematically characterized. This review aimed to comprehensively explore how miRNAs that target the HIV-1 genome simultaneously modulate key innate and adaptive host immune signaling pathways. The conceptual novelty of this study is determined not by the identification of previously unknown miRNA-target gene pairs, but by the systemic integration of two regulatory levels (direct inhibition of the viral genome and modulation of the host cell immune signaling pathways) within a unified analytical framework. Such an integrated approach reveals a proviral regulatory network that remains non-obvious when each of these levels is examined separately. Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar (all years through 2025). In Stage 1, publications reporting experimentally confirmed interactions between host miRNAs and the HIV-1 genome were identified, yielding a curated set of 15 miRNAs. In Stage 2, target genes for each miRNA were retrieved from miRTarBase, TarBase (experimentally validated) and TargetScan 8.0 (in silico predicted). In Stage 3, target genes were manually mapped to key immune signaling pathways (TLR, NF-κB, JAK-STAT). In Stage 4, targeted literature searches were performed for each miRNA–target gene pair to identify direct experimental evidence of interaction. All stages were performed by two independent researchers, with discrepancies resolved by a third. Results: Fifteen host miRNAs with experimentally confirmed binding to the HIV-1 genome were identified, targeting viral genes including nef, pol, vpr, gag, env, vif, and the 3′-UTR. Thirteen of these miRNAs were found to regulate components of major immune pathways. miR-92a-3p, miR-29a/b-3p, miR-150-5p, and miR-125b-5p emerged as the most pleiotropic regulators, simultaneously suppressing TLR signaling (TLR3, TLR7, TLR8, MyD88, TRAF3/6, IRAK1/4), NF-κB components (REL, RELA, NFKB1), JAK-STAT effectors (STAT1–3, STAT5A/B, JAK2), and negative regulators of cytokine signaling (SOCS and PIAS family proteins). miR-133b and miR-196b-5p were found to selectively regulate SOCS/PIAS proteins without involvement in other analyzed pathways, suggesting potential for selective therapeutic targeting. Conclusions: The analyzed miRNAs exhibit functional dualism, acting as direct post-transcriptional suppressors of the HIV-1 genome while simultaneously functioning as epigenetic modulators of host immune signaling. These two modes of action are not independent but together form a conceptual framework of a self-reinforcing proviral regulatory network that, based on the synthesis of published evidence, is proposed to promote viral latency and immune evasion. The identified miRNAs represent promising, albeit complex, targets for novel therapeutic strategies aimed at eliminating latent HIV reservoirs. Full article

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1), driven by high mutation and recombination rates, poses significant challenges for diagnostics, therapy, and vaccine development. While variable regions enable immune escape, hyperconserved regions are critical for viral function and represent promising targets for novel therapeutic interventions. This study aimed to develop and validate a bioinformatic algorithm for quantitative assessment of sequence conservation and automated identification of functionally significant conserved regions across all major HIV-1 proteins. A total of 1119 full-length HIV-1 genome sequences representing major subtypes (A1, A2, A6, B, C, D, F1, F2, G, H, J, K) were analyzed. Normalized Shannon entropy (S-index) was calculated for each alignment column. Statistical thresholds for conserved regions were established using 95% confidence intervals derived from bootstrap resampling. Two complementary algorithms, clustering and local maxima detection, were applied to identify conserved regions, which were subsequently mapped to known functional domains based on literature data. Protein conservation varied markedly, with S_m values ranging from 0.784 (Vpu) to 0.920 (Pol). Gag, Pol, and Vpr demonstrated the highest overall conservation, while Env, Rev, Tat, and Vpu exhibited pronounced variability interspersed with conserved domains. In total, 25 conserved regions in Gag, 49 in Pol, 28 in Env, and 6–4 regions in accessory proteins (Vif, Vpr, Rev, Tat, Nef, Vpu) were identified. These regions corresponded to critical functional elements including enzyme catalytic centers, zinc fingers, receptor-binding sites, protein interaction interfaces, and membrane-anchoring domains. The developed computational framework enables statistically grounded identification of evolutionarily constrained regions across analyzed HIV-1 subtypes. The identified conserved regions represent candidate sites for further investigation and may inform downstream studies focused on antiviral target prioritization, immunogen design, and diagnostic assay development. However, their translational applicability requires additional analytical, structural, and experimental validation. Full article