Search Results (2,172)

The inherent genomic plasticity of RNA viruses, particularly influenza viruses and SARS-CoV-2, poses a major obstacle to the establishment of durable herd immunity. This challenge is further compounded by immune imprinting, whereby prior antigenic exposures bias subsequent responses toward previously encountered epitopes at the expense of effective recognition of antigenically drifted variants. In this review, we delineate the mechanistic basis of immune imprinting, with emphasis on the competitive dominance of cross-reactive memory B cells (MBCs). We discuss how the rapid “back-boosting” of these pre-existing clones can limit de novo priming of naïve B cells—through epitope masking and competition for antigen and T follicular helper cell support—thereby diverting germinal center selection and affinity maturation away from variant-specific de novo epitopes and promoting viral immune escape. To address this challenge, this article further reviews the characteristics of immune imprinting responses in influenza viruses, coronaviruses, and dengue virus, as well as corresponding countermeasures, providing a theoretical basis and new avenues for intervention to address immune imprinting induced by rapidly mutating RNA viruses. Full article

Seasonal epidemics and high variability of influenza viruses pose a severe threat to global public health security. Neuraminidase, a key functional enzyme in the life cycle of influenza viruses, represents an important target for anti-influenza drug development. Given the continuous emergence of drug-resistant strains against first-line clinical neuraminidase inhibitors (NAIs) such as oseltamivir, there is an urgent need to develop novel, broad-spectrum, and resistance-overcoming NAIs. Natural products, characterized by structural diversity and a wide range of biological activities, provide abundant resources for the discovery of new NAIs. Recent advances in computer-aided drug design, intelligent analytical platforms, and modern screening technologies have accelerated the identification of natural product-derived NAIs. In particular, biosensor-based strategies, including electrochemical, fluorescence, bioluminescence, and surface-enhanced Raman scattering biosensors, have demonstrated significant advantages in sensitivity, selectivity, rapid response, and high-throughput screening. In combination with computational methods and experimental approaches such as affinity ultrafiltration and activity-guided separation, these technologies have promoted the development of intelligent, precise, and multimodal screening platforms. Looking forward, the integration of biosensor-based high-throughput screening platforms with artificial intelligence algorithms is expected to drive the next generation of natural product screening platforms and facilitate the efficient discovery and clinical translation of novel NAIs. This paper systematically reviews the research progress of screening strategies for natural product-derived NAIs; introduces representative natural active NAIs, including phenols, terpenoids, and alkaloids; and prospects future development directions, aiming to provide a scientific reference for the efficient discovery of NAIs from natural products. Full article

Avian influenza viruses (AIVs) are widely distributed and have a wide range of hosts. Recently, the number of cases of infection associated with the circulation of highly pathogenic avian influenza H5N1 2.3.4.4b has raised concerns about its high transmission capacity in birds and mammals. This study analyzed swabs from bird and mammal species from the coast of Paraná and the northwest region of São Paulo, Brazil, for the presence of AIV in animals that did not present clinical or histopathological lesions of infection that indicated the need for molecular characterization during monitoring. Of the 661 animals analyzed, three tested positive, two of which were birds (Sula leucogaster and Thalasseus acuflavidus) while one was a mammal (Otaria flavescens) (0.45%, CI 95%: 0.16–1.33). A complete genome sequence of H5N1 AIV was obtained from a brown booby (Sula leucogaster) from the Paraná coast (GISAID accession number: EPI_ISL_1897537). Our study reinforces the importance of continuous genomic surveillance, especially in AIV hosts that do not show signs of infection, to enhance the One-Health assessment approach. Full article

Background: Influenza remains a major global public health threat, and vaccination is one of the most effective preventive measures. However, frequent antigenic drift and occasional antigenic shift, along with the lead time required for vaccine development and regional differences in the evolution of circulating strains, may lead to mismatches between WHO-recommended vaccine strains and circulating viruses. In addition, antiviral resistance further complicates precise influenza prevention and control. Objectives: This study aimed to evaluate the concordance of vaccine strains with circulating influenza viruses and the emergence of neuraminidase inhibitor (NAI) resistance in China. Methods: Data on antigenic characterization and antiviral susceptibility testing were extracted from weekly influenza surveillance reports published by the Chinese National Influenza Center from 2015 to 2025. Viral evolution, substitutions at key antigenic sites, and resistance-associated mutations were further examined based on sequences of circulating influenza viruses in China. Results: The overall vaccine match rates were 95.72% (95% CI: 94.02–97.43%) for A(H1N1)pdm09, 58.96% (95% CI: 54.93–62.96%) for A(H3N2), 64.45% (95% CI: 59.49–69.41%) for B/Victoria, and 95.19% (95% CI: 91.32–99.05%) for B/Yamagata in China during the 2015–2025 influenza seasons, with marked year-to-year fluctuations observed particularly for A(H3N2) and B/Victoria. The vaccine matching for cell-based A(H3N2) (70.41%, 95% CI: 65.04–75.77%) vaccine reference strains was significantly higher than that for egg-based A(H3N2) (48.09%, 95% CI: 42.63–53.55%) vaccine reference strains. Sequence analysis indicated that circulating A(H3N2) viruses showed the greatest genetic divergence from the matched egg-based vaccine strains (2.71%, 95% CI: 2.66–2.75%). Phenotypic NAI resistance was detected only in A(H1N1)pdm09 viruses, with resistance rates of 0.18% (95% CI: 0.07–0.45%) in 2023, 3.47% (95% CI: 2.63–4.57%) in 2024, and 3.01% (95% CI: 2.46–3.68%) in 2025. Neuraminidase (NA) sequence analysis showed that the key NAI resistance-associated substitution H274Y has been detected in A(H1N1)pdm09 viruses since 2015, at relatively high frequencies observed during 2015–2018. The mutation re-emerged in 2023 and presented increase trends thereafter, although no A(H1N1) pdm09 circulated during the COVID-19 pandemic. Conclusions: Antigenic concordance between vaccine strains and circulating A(H3N2) or B/Victoria viruses showed marked year-to-year fluctuations in China. Cell-based A(H3N2) vaccine reference strains showed higher antigenic concordance than egg-based strains, supporting further consideration of vaccine production platforms in A(H3N2)-predominant seasons. Phenotypic NAI resistance in circulating A(H1N1)pdm09 viruses was detected from 2023 onward in China, whereas resistance-associated NA substitutions had been detected earlier at the sequence level. Full article

Avian influenza viruses continue to pose significant zoonotic and pandemic threat globally, with low-pathogenic avian influenza A(H9N2) being of particular concern due to sustained circulation in poultry, adaptability, and repeated human spillover. This study investigated the detection and genetic characterization of influenza viruses at the animal–human interface in Ghana in 2022, using a nationwide cross-sectional One Health approach. Samples were collected from poultry, pigs, the environment, and animal handlers across backyard farms, commercial farms, and live bird markets. Laboratory testing was conducted using real-time RT-PCR, while statistical associations were assessed using chi-square and logistic regression. Whole-genome sequencing and phylogenetic analysis were performed on selected positive samples. Out of 4056 samples, 1516 were poultry samples. A(H9N2) was detected exclusively in poultry, with a prevalence of 5.67%. The Northern belt recorded the highest prevalence. Live bird markets had significantly higher odds of A(H9N2) detection compared with commercial farms (odds ratio: 15.37, p < 0.0001), while backyard farms had lower odds. Environmental samples were negative. Among animal handlers, one case each of A(H3N2) and SARS-CoV-2 was identified. Phylogenetic analysis demonstrated that Ghanaian strains belonged to clade G1 and possessed mammalian-adaptive markers. These findings highlight ongoing circulation in poultry and the need for sustained One Health surveillance. Full article

The co-circulation of respiratory viruses, including SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV), represents a significant global health challenge that requires rapid, accurate, and differential diagnosis to support infection control and appropriate clinical decision-making. This narrative review summarizes emerging multimodal point-of-care testing (POCT) strategies for the detection and management of these respiratory viruses. Relevant studies were identified through literature searches of major scientific databases, including PubMed, Scopus, and Web of Science, focusing on recent advances in molecular diagnostics, biosensors, microfluidics, and digital health technologies. To improve clinical interpretation and comparative assessment, current POCT platforms were organized into four operational tiers based on infrastructure dependence, degree of portability, and level of decentralization of testing. Tier 1 (Professional Clinical Systems) includes fully integrated automated molecular diagnostic platforms designed for use in hospital and emergency care settings. Tier 2 (Field-Deployable Systems) comprises portable molecular and isothermal amplification technologies designed for use in decentralized or resource-limited environments. Tier 3 (Hardware-Lite Assays) includes simplified diagnostic approaches that minimize instrument requirements and are suitable for near-patient or low-infrastructure settings. Tier 4 (Consumer-Digital Diagnostics) encompasses emerging smartphone- and IoT-integrated diagnostic platforms that support user-driven testing and digital health connectivity. This tier-based framework reflects a proposed stratification of POCT technologies along a decentralization continuum and aims to facilitate comparison and selection of diagnostic strategies across diverse healthcare settings. Full article

Influenza B virus (IBV) represents a significant global health threat, contributing 20–30% of annual influenza cases and causing substantial morbidity and mortality across all age groups. Current seasonal vaccines demonstrate variable effectiveness, highlighting the urgent need for next-generation approaches that provide enhanced and sustained protection against both IBV lineages. Moreover, continuous antigenic drift of circulating viruses progressively reduces the match between vaccine-induced antibodies and contemporary strains, necessitating broad-spectrum protection strategies. This review discusses influenza B virus control strategies, encompassing both conventional approaches and emerging vaccine technologies. While antiviral therapy, epidemiological surveillance, diagnostics, and non-pharmaceutical public-health measures are integral components of influenza B control, the present review focuses specifically on vaccine-based strategies. By critically appraising the available evidence, this review evaluates the extent to which these strategies may improve the effectiveness of IBV vaccines and, in the longer term, inform the prospect of reducing the burden of—or potentially eliminating—influenza B virus, a goal that remains hypothetical and requires clinical validation. Full article

This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article

Influenza viruses, due to their simple genomic structure and potent immunostimulatory capacity, have been extensively explored for applications in cancer immunotherapy and viral vector vaccine development. However, wild-type influenza viruses possess inherent risks of lethal pathogenicity and transmissibility, which limit their direct application. Special cold-adapted influenza strains have been widely used in live attenuated vaccines, which rely on specific amino acid mutations. With the advancement in synthetic biology and reverse genetics technologies, a variety of next-generation attenuated influenza virus have been developed, including genome-recoded viruses, miRNA-targeted viruses, viruses containing premature termination codons, and proteolysis-targeting recombinantviruses. This study systematically summarized the synthetic biology-based strategies for generating a next-generation method for the attenuated influenza virus, critically discussed the advantages and limitations of each strategy, and further analyzed their applications and challenges in cancer therapy and viral vector vaccine development. By synthesizing current research progress, this review aimed to provide a theoretical basis for constructing safer, more stable, and more controllable influenza virus engineering platforms, and to offer new insights for the design of attenuated influenza virus suitable for tumor therapy and novel vaccine delivery. Full article

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses of clade 2.3.4.4b have recently spread across the Americas, prompting intensified surveillance efforts in Brazil aimed at early detection in wild birds. As part of these efforts, we identified a low pathogenic avian influenza A(H11N2) virus in a white-rumped sandpiper (Calidris fuscicollis) sampled at Lagoa do Peixe National Park (PNLP) in southern Brazil. Whole-genome sequencing revealed that seven of the eight gene segments shared high nucleotide similarity (approximately 98.8%) with viruses previously detected in shorebirds from Delaware Bay, North America. In contrast, the PB1 segment showed high nucleotide similarity (approximately 99%) to the PB1 lineage associated with clade 2.3.4.4b A(H5N1) genotype B3.2 viruses circulating in the Americas. Phylogenetic, nucleotide identity, and molecular clock analyses indicated that this lineage shares a recent common ancestor with North American LPAI viruses and was subsequently detected in distinct viral genetic backgrounds. Although no HPAI virus was identified in this study, the presence of a PB1 segment related to H5N1-associated lineages suggests that genetic components linked to these viruses were circulating among low pathogenic avian influenza viruses in South America. These findings highlight the importance of continued surveillance in migratory bird populations to improve understanding of avian influenza virus diversity and support epidemiological monitoring. Full article

Influenza viruses continue to pose a significant threat to both animal and public health due to their rapid evolution and the frequent emergence of antiviral resistance. Host-directed antiviral (HDA) strategies, which target host factors essential for viral replication, may represent an alternative to conventional virus-targeting approaches. However, the identification of reliable and therapeutically actionable host targets remains a major challenge, primarily due to the complexity and context dependency of host–virus interactions. Recent advancements in multi-omics technologies, including functional genomics, transcriptomics, and proteomics, have facilitated the systematic characterization of host factors involved in influenza virus infection. These methodologies have unveiled intricate regulatory networks that govern viral replication and host immune responses. Nonetheless, translating large-scale datasets into biologically meaningful targets necessitates robust integrative frameworks. In this context, artificial intelligence (AI) and machine learning methods offer powerful tools for data integration, target prioritization, and predictive modeling. In this Review, we summarize current insights into host factors that regulate influenza virus infection and discuss how multi-omics and AI-driven approaches are expediting host target discovery. Furthermore, we highlight the potential of these strategies to enhance antiviral development while addressing key challenges related to specificity, safety, and translational application. Collectively, these advancements lay a foundation that may support the rational design of next-generation host-directed antivirals. Full article

Background/Objectives: Emerging viral zoonoses represent a growing threat to global public health, with most newly emerging infectious diseases originating from animal reservoirs. Recent outbreaks of monkeypox, Ebola virus disease, Marburg virus disease, Rift Valley fever, and avian influenza highlight the capacity of zoonotic viruses to cross species barriers, spread internationally, and generate substantial health, social, and economic consequences. This review examines the ecological, epidemiological, and biological determinants of viral zoonotic emergence and transmission, with particular emphasis on vaccination and outbreak prevention strategies. Methods: A structured narrative review was conducted using a predefined literature search strategy across major scientific databases. Peer-reviewed epidemiological, clinical, and public health publications published between January 2000 and February 2026 were screened and selected according to predefined relevance criteria. Results: The emergence of viral zoonoses is driven by complex interactions among animal reservoirs, environmental and climatic changes, human behavior, and viral adaptation. Although transmission pathways and clinical outcomes differ among pathogens, common determinants of spillover and outbreak amplification were identified. Current evidence supports the importance of integrated surveillance, genomic monitoring, vaccination strategies, and community engagement as key components of preparedness and response. Emerging preventive approaches targeting pathogen transmission, including transmission-blocking strategies and vector-associated microbiota interventions, may provide additional opportunities for disease control. Conclusions: Strengthening preparedness for emerging viral zoonoses requires coordinated One Health approaches integrating human, animal, and environmental health. Future priorities include the development of next-generation vaccines, expansion of digital and genomic surveillance systems, improved equitable access to vaccines, and innovative interventions aimed at reducing zoonotic spillover and interrupting pathogen transmission. Full article

Mucosal immunity in the respiratory tract provides the first line of defense against airborne pathogens, yet most current vaccines fail to induce strong and durable immune responses at these sites. Respiratory viruses, including respiratory syncytial virus (RSV), influenza viruses, and coronaviruses, remain major global health threats, in part due to their ability to evade long-term mucosal protection. Although systemic vaccination generates robust circulating immunity, it induces limited local responses, particularly secretory immunoglobulin A (IgA), which is critical for preventing viral entry and transmission at the airway surface. The mechanisms regulating B cell responses within the airway mucosa are not fully understood. B cell–activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, has emerged as an important context-dependent regulator of mucosal B cell immunity. BAFF is produced by airway epithelial cells and multiple myeloid populations, including dendritic cells and neutrophils, and is rapidly induced during respiratory viral infection through type I interferon–dependent pathways. Functionally, BAFF supports B cell survival, differentiation, and class-switch recombination, promoting the generation of antibody-secreting plasma cells and enhancing IgA production. In the lung, these effects align with early, intermediate, and late stages of the response, supporting initial local antibody production, the formation of inducible bronchus-associated lymphoid tissue (iBALT), and the development of tissue-resident memory B cells that sustain long-term immunity. Although BAFF plays an essential role in mucosal immunity, its activity requires tight regulation to maintain immune balance. Current evidence supports BAFF as a promising immunomodulatory component and highlights its potential as an adjuvant platform for enhancing mucosal vaccine efficacy, warranting further investigation as a potential adjuvant in this context. Full article

Avian influenza remains a major threat to poultry production, wildlife conservation, and public health in Asia, where migratory birds, wetlands, rice paddies, domestic ducks, and live poultry trade often intersect. This Asia-focused review synthesizes ecological, epidemiological, surveillance, tracking, phylogenetic, and environmental evidence from 1996 to 2025, with particular emphasis on China, to clarify how risk develops at the wild bird–domestic poultry interface. The reviewed evidence suggests three broad epidemic phases: early Goose/Guangdong-lineage H5N1 outbreaks before 2014, recurrent clade 2.3.4.4 H5Nx expansions during 2014–2019, and the widespread clade 2.3.4.4b H5N1 period since 2020. Spatial risk is concentrated around major stopover wetlands and rice-paddy–duck landscapes, including Qinghai Lake, Poyang Lake, Sanmenxia, the Sanjiang Plain, and peri-urban market belts. Wetlands and paddies can maintain viruses environmentally, free-grazing ducks and bridge hosts can facilitate introduction, and live poultry markets and trade networks can amplify and export risk. By organizing these processes through an Interface–Amplifier–Conduit evidence-mapping approach, this review highlights setting-specific priorities, including seasonal wetland surveillance, closed farm-water systems, improved market hygiene, and better integration of ecological and genomic data for early warning and control. Full article

Background: Following the coronavirus disease 2019 (COVID-19) pandemic, increased reports of severe acute hepatitis of unknown etiology in children have raised concerns about virus-associated liver injury. Acute respiratory tract infections (ARTIs) are a common cause of pediatric hospitalization and may be accompanied by reactive hepatitis; however, virus-specific patterns of hepatic involvement remain incompletely defined. This study aimed to evaluate liver involvement associated with ARTIs in hospitalized children. Methods: This retrospective study included pediatric patients (<18 years) hospitalized with ARTIs between October 2021 and May 2023. Respiratory viruses were identified via multiplex real-time polymerase chain reaction assays. Liver function tests were systematically evaluated during hospitalization. Transaminase elevations were categorized according to the upper limit of normal (ULN = 40 U/L). Acute hepatic failure was defined according to the Pediatric Acute Liver Failure criteria. Results: A total of 179 patients were analyzed (median age: 38 months; 59.2% male). Elevated AST and ALT levels were observed in 24.0% and 8.4% of patients, respectively. Adenovirus was the most frequently detected virus (11.2%), followed by influenza A (7.3%) and parainfluenza virus (6.7%). Severe transaminase elevations (>5 × ULN and >500 U/L) were observed in patients with influenza infection. All cases of acute hepatic failure (n = 3) were associated with influenza infection. Other respiratory viruses were associated with mild or transient liver enzyme abnormalities. Conclusions: Severe hepatic involvement—including severe transaminase elevation and acute hepatic failure—occurred exclusively in children with influenza infection, particularly influenza B, while mild and transient liver enzyme abnormalities were common across other respiratory viral infections. These findings highlight the importance of targeted liver function monitoring in pediatric influenza patients and provide clinically relevant data on virus-specific hepatic involvement in the post-COVID-19 era. Full article