Search Results (918)

Influenza (flu) is a common respiratory virus with seasonal global spread. Zoonotic viruses can occasionally cross species, leading to pandemic-level spread, and for flu viruses, this is considered an “antigenic shift”. The flu can be particularly severe during pregnancy due to immune system adaptations that occur during pregnancy, with prior global pandemics causing excess hospitalizations, deaths, and other complications in the mothers and the neonates. We aim to review the current literature with respect to novel avian H5N1 and the potential impact of infection with flu during pregnancy. A systematic literature search was conducted. Here we provide a rapid summary of epidemiology and understanding of viral spread, published risks of H5N1 in pregnancy, the unique physiologic, cellular, and molecular adaptations making H5N1 infection unique in pregnancy, implementation of an effective vaccine program in event of a pandemic specific to pregnant individuals, optimizing peripartum care for infected individuals, and direction for future research to direct vaccine strategy and mitigate risks in a future flu pandemic. Full article

Despite the persistent global threat of seasonal influenza viruses such as A(H1N1)pdm09 and A/H3N2, their epidemiological and genetic characteristics in China following the implementation of COVID-19 non-pharmaceutical interventions (NPIs) remain poorly characterized. Between September 2020 and December 2023, we conducted an integrated epidemiological and genomic analysis of influenza A viruses in children in Wuhan. The overall positivity rate for influenza A virus was markedly low at 3.43% (109/3171), reflecting a profound suppression of circulation during the pandemic. Among genotyped positives, H1N1pdm09 was predominant (52.3%), followed by H3N2 (16.5%) and untypeable strains (32.1%). Preschool children showed the highest susceptibility. Phylogenetic analysis revealed that the circulating H1N1 strains (90%) belonged to clade 6B.1A.5a.2, clustering with viruses from Hong Kong and Pakistan. In contrast, H3N2 strains (76.92%) primarily fell into clade 3C.2a1b.2a.2b, closely related to contemporary strains from Europe and North America. Notably, we identified key hemagglutinin mutations associated with antigenic drift (e.g., R240Q in H1N1; E78G, R158G in H3N2) and neuraminidase mutations potentially conferring antiviral resistance (e.g., S247N in H1N1; S245N, a putative novel glycosylation site, in H3N2). Evidence of reassortment events was also detected, underscoring the continued genomic evolution of these viruses despite their low prevalence. Our findings demonstrate that genetically diverse and antigenically drifted influenza A viruses continued to circulate and evolve in Wuhan during the COVID-19 pandemic, albeit at dramatically reduced levels. This highlights the critical need for sustained genomic surveillance and timely updates of vaccine compositions to pre-empt the resurgence of influenza in the post-pandemic era. Full article

Influenza A viruses constantly threaten the global population, with seasonal outbreaks occurring in different parts of the world, including avian influenza. Severe influenza A virus infections are strongly associated with the cytokine storm, which can contribute significantly to morbidity and even mortality. The virulence and high mutability of these viruses necessitate more effective treatment strategies and regimens to manage patients, especially those with a severe disease. Favipiravir is an antiviral agent approved in Japan for treating influenza virus strains resistant to the current antivirals. The objective of this study is to investigate the combination treatment of Favipiravir paired with selected repurposed drugs to determine the effectiveness of these combinations against influenza A virus replication as well as their effects on cytokine expression. Specific combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin were identified to be highly synergistic and effective in inhibiting live virus titers of an influenza H3N2 clinical strain by 4 log₁₀. Furthermore, combinations of Favipiravir with Doxycycline or Azithromycin also exhibited immunomodulatory effects on pro-inflammatory cytokines by strongly reducing the relative mRNA expression of IFN-γ, IL-6, TNF-α and IL-1β. Notably, monotherapy with Andrographolide also completely inhibited influenza virus titers by 4 log₁₀. Specific combinations of Favipiravir with Artesunate or Andrographolide revealed additive effects by inhibiting influenza virus titers by about 2 or 1.5 log₁₀, respectively. Our findings indicate that specific drug combinations show promising efficacy and potential in the treatment of influenza and warrant further studies using influenza models of human cell, tissue and animal infection. Full article

The highly pathogenic avian influenza virus (HPAIV) is widely distributed worldwide and causes significant economic losses. Transmission of HPAIV occurs through direct contact between infected and susceptible birds or indirectly via contaminated materials. In recent years, airborne transmission of HPAIV has also been reported, underscoring the need for novel approaches to effectively inactivate airborne HPAIV. Photocatalysts have attracted significant attention as potential antiviral agents. In this study, we demonstrated that a TiO₂-mediated photocatalytic reaction inactivated HPAIV and H1N1 seasonal influenza viruses in liquid, reducing their infectivity by 90.7% and 94.4%, respectively, after 60 min. Mechanistic analyses revealed decreased virion size and surface structure disruption, as determined by transmission electron microscopy. Additional evidence of viral protein and genome damage was obtained using Western blotting and RT-qPCR, respectively. Given the broad antiviral activity of photocatalysts, these findings suggest that they can inactivate influenza viruses regardless of strain or subtype. Notably, photocatalysts inactivated 80% of aerosolized H1N1 seasonal influenza viruses within 5 min. These results provide strong evidence that photocatalysts are capable of inactivating airborne influenza viruses. This study represents the first demonstration that photocatalysts can inactivate HPAIV and aerosolized influenza viruses. These findings provide strong evidence that photocatalysts represent a promising countermeasure against HPAIV, with potential applicability across different strains and subtypes. Full article

Polymerase chain reaction (PCR) is the primary method for virus detection; however, its complex preprocessing has prompted research into simpler immunoassay-based approaches. Among these, techniques using antibody-modified magnetic particles, exemplified by digital ELISA, provide ultra-high sensitivity comparable to PCR by efficiently capturing trace viruses and enabling concentration, washing, and transfer to microreactors. In this study, we evaluated the virus capture efficiency of antibody-modified magnetic particles based on quantitative PCR (qPCR). Influenza A virus (H1N1/A/Puerto Rico/8/1934) was tested with 1 μm magnetic beads modified with HA1 antibodies. As quantification becomes unreliable and difficult in an extremely low-concentration range near the detection limit of qPCR, low-concentration viral suspensions (10⁵ copies/mL) were mixed with particle dispersions (up to 5 × 10⁸ particles/mL) for 10 min, followed by magnetic separation and washing, and the remaining virus in each fraction was analyzed by qPCR. At the highest particle concentration, capture rates exceeded 80% relative to the initial suspension, indicating near-complete capturing when considering free nucleic acids. Time-course analysis showed that the capture rate reached saturation within 2 min, with approximately 90% of the saturation at 1 min. Furthermore, kinetic modeling of magnetic bead–virus binding reproduced experimental data. These findings demonstrate that short mixing times with high particle concentrations enable efficient virus capture, contributing to the development of rapid and highly sensitive immunoassay systems. Full article

Avian influenza (AI) significantly threatens poultry health and causes major economic losses in the poultry industry. Vaccination remains crucial for AI prevention and control. The major protective epitopes of influenza viruses are located on hemagglutinin (HA), a surface glycoprotein essential for viral infection. Most influenza vaccines induce neutralizing antibodies against HA to block viral entry. HA maturation requires the HA0 precursor to be proteolytically cleaved at a conserved site by host proteases to yield HA1 and HA2 subunits. A subsequent acidic condition triggers HA conformational changes, enabling viral–host membrane fusion. However, whether HA conformational variations affect immunogenicity remains unclear. In this study, the cleavage site of the HA gene from an H9N2 avian influenza virus was modified to block the proteolytic cleavage of the HA protein. Our results revealed distinct proteolytic patterns of certain mutants, which exhibited either increased or decreased cleavage efficiencies compared to the wild-type (WT) HA. However, none of the mutants exhibited completely abolished HA0 cleavage. To assess the immunogenicity of these variants, BALB/c mice were immunized with DNA vaccines expressing either WT or mutant HA proteins. Strikingly, the mutant HA protein with a 19-amino-acid deletion Dlt5 (P6~P1, P1’~P′13) at the cleavage site exhibited reduced cleavage efficiency and induced significantly higher HI antibody titers compared to the WT. These results offer valuable perspectives for enhancing avian influenza vaccine efficacy through strategic modification of HA cleavage properties. Full article

Influenza viruses are characterized by their high mutation rates which require continuous molecular surveillance to ensure the annual effectiveness of influenza vaccines. The current study aimed to investigate the molecular evolution and vaccine match of the 2009 pandemic (A(H1N1) pdm09) virus circulating in Riyadh, Saudi Arabia. A total of 380 nasopharyngeal aspirates (NPAs) were collected during the 2020–2023 winter seasons from patients with influenza-like illness. Influenza A virus (IAV) detection, typing, and amplification of hemagglutinin (HA) and neuraminidase (NA) genes were achieved using one-step RT-PCR. The full-length HA and NA genes of 14 selected A(H1N1) pdm09 isolates were sequenced and used for sequence and phylogenetic analysis, which also included sequences of seven A(H1N1) pdm09 isolates collected in Riyadh during the 2024–2025 season. IAV was detected in 17.11% samples; A/H3N2 (9.21%) was somewhat more prevalent than A(H1N1) pdm09 (7.89%). Children aged 0–4 years had the highest incidence rate of infection. Comparing the HA1 domain of A(H1N1) pdm09 isolates circulating in Riyadh to the current vaccine strains (A/Wisconsin/67/2022 and A/Victoria/4897/2022), a total of 24 amino acid substitutions were identified. O-linked and N-linked glycosylation sites in the HA and NA proteins of the Riyadh isolates coincided with those of the two vaccine strains. The receptor-binding domain (130-loop) of the HA1 domain showed a persistent S137P substitution in all study isolates; this mutation is not present in the current vaccination strain. This finding suggests a potential antigenic mismatch between the current vaccine and the circulating A(H1N1) pdm09 strains in Riyadh, warranting hemagglutination inhibition (HAI) assays to confirm the impact of the S137P substitution on antigenicity and immune evasion. As shown above, ongoing molecular surveillance is essential for guiding the yearly selection of vaccine candidates to increase efficacy. Full article

Background: Airway bacterial infection and inflammation are often present in children with bronchiectasis. Systemic inflammation has also been reported. Currently, there are no data on the association between systemic inflammatory markers with airway pathogens or neutrophilia in children with bronchiectasis. We aimed to define the bronchoalveolar lavage (BAL) pathogens (bacteria and viruses), and cytology in children with bronchiectasis and to explore any association between peripheral inflammatory markers and airway neutrophilia. Methods: Participants numbering 402, aged <18 years, with peripheral blood and BAL results within 3 months of diagnosis of bronchiectasis were included. Blood and BAL results were reviewed and analysed for possible associations. Results: Of 355 children (88.31%), cultured bacteria from BAL and Haemophilus influenzae (n = 185) were the most frequent. A virus was identified in 131 (32.59%). Adenovirus (n = 69) was most common. Children numbering 279 (69.40%) had airway neutrophilia (neutrophils > 15%) which was associated with the presence of H. influenzae (OR 2.03 95% CI 1.31–3.15, p = 0.002), S. pneumonia 2.41 (95% CI 1.36–4.29, p = 0.003), and Adenovirus (OR 2.06 95% CI 1.06–4.04, p = 0.033). Airway neutrophilia was associated with raised CRP (OR 2.26 95% CI 1.14–4.49, p = 0.019), but there were no other systemic inflammatory markers including monocyte/lymphocyte ratio, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and platelet/mean platelet volume ratio. Conclusions: In children, there is an association between airway neutrophilia and raised CRP in bronchiectasis, but not with other peripheral inflammatory markers. There is a need to identify non-invasive inflammatory markers in children with bronchiectasis. Full article

Infectious pathogens pose serious threats to public health, necessitating the development of more antimicrobials. In this study, oligohydroxybutyrates were obtained through the catalyzed polymerization of β-butyrolactone using N, N-dimethyl-4-aminopyridine (DMAP) and aluminum isopropoxide [Al(OiPr)₃] and applied as sustainable antimicrobial agents. The poly3-hydroxybutyrate (PHB) oligomers exhibited broad-spectrum antibacterial activities against both Gram-negative (E. coli) and Gram-positive (S. aureus) model bacteria. Additionally, PHB oligomers displayed robust (inhibiting rate: >95%) and rapid (action time: <20 min) antiviral activity against three notorious single-stranded RNA viruses, that is, influenza A virus (H1N1 and H3N2) and coronavirus (SARS-CoV-2). In particular, a comprehensive set of advanced experimental characterizations, including FT-IR, ¹H- and ¹³C-NMR, and H-ESI-MS/MS, was applied to analyze their chemical structures. The results confirmed the loss of terminal hydroxyl groups in the PHB intermediate and end products associated with theoretical calculations. These findings will also help provide deep insight into the major chain growth mechanism during the synthesis of PHB. The structural variations, which were treated as unwanted side reactions, were identified as a pivotal factor by deactivating the terminal hydroxy during chain growth. Their effective sterilization properties and degradability endowed the as-prepared PHB oligomers with a promising biomedical potential, including for use as disinfectants, sanitizers, and antiseptics. Full article

Influenza A viruses exhibit broad host tropism, infecting multiple species including humans, avian species, and swine. Swine influenza virus (SIV), while primarily circulating in porcine populations, demonstrates zoonotic potential with sporadic human infections. In this investigation, we identified two H1N1 subtype swine influenza A virus strains designated A/swine/China/SD6591/2019(H1N1) (abbreviated SD6591) and A/swine/China/SD6592/2019(H1N1) (abbreviated SD6592) in Shandong Province, China. The GenBank accession numbers of the SD6591 viral gene segments are PV464931-PV464938, and the GenBank accession numbers corresponding to each of the eight SD6592 viral gene segments are PV464939-PV464946. Phylogenetic and recombination analyses suggest potential evolutionary differences between the isolates. SD6591 displayed a unique triple-reassortant genotype: comparative nucleotide homology assessments demonstrated that the PB2, PB1, NP, NA, HA, and NEP genes shared the highest similarity with classical swine-origin H1N1 viruses. In contrast, SD6592 maintained genomic conservation with previously characterized H1N1 swine strains, although neither of these two isolates exhibited significant intrasegmental recombination events. Through comprehensive sequence analysis of these H1N1 SIVs, this study provides preliminary insights into their evolutionary history and underscores the persistent risk of cross-species transmission at the human–swine interface. These findings establish an essential foundation for enhancing national SIV surveillance programs and informing evidence-based prevention strategies against emerging influenza threats. Full article

Avian influenza viruses are predominantly associated with waterfowl and shorebirds, and are rarely detected in other avian hosts in nature. In 2021, an H1N1 virus was isolated from a Fieldfare Turdus pilaris in Zaporizhzhia Oblast, Ukraine. A phylogenetic analysis revealed that all eight gene segments belonged to the Eurasian low-pathogenic avian influenza lineages. The highest nucleotide identity of the HA gene was observed with viruses detected in Georgia, Sweden, and Ukraine (99.11%), while the NA gene showed the greatest identity to viruses from Western Europe (99.14–99.57%). Genetic analysis of the HA cleavage site showed a sequence (PSIQSR↓GLF) that contained a single basic amino acid. No deletions were detected in the stalk region of NA gene, and no specific mutations in PB2 protein were found. However, several amino acid substitutions were identified in the HA gene (D204E, S207T, and D239G) that may affect the binding affinity to specific antibodies. The occurrence of this virus in a wild, seemingly healthy thrush indicate that additional surveillance in poorly studied ecological groups such as Passeriformes is warranted. Full article

The endemicity of H9N2 avian influenza viruses (AIVs), particularly the Y280 lineage, poses persistent challenges to the poultry industry due to the limitations of inactivated vaccines, such as interference by maternally derived antibodies (MDAs) and incomplete suppression of viral replication. This study evaluated the immunogenicity and protective efficacy of a novel recombinant turkey herpesvirus vaccine expressing the hemagglutinin gene of H9N2/Y280 (rHVT-H9/Y280) in commercial Hy-Line Brown layers with high-MDA backgrounds. In a comparative challenge study, the rHVT-H9/Y280 vaccine induced complete protection against a homologous Y280 strain challenge at 4 weeks of age, whereas commercial inactivated vaccines failed to completely block replication, showing virus isolation rates of 16.7–25%. Long-term serological monitoring demonstrated that the rHVT-H9/Y280 vaccine elicited a robust humoral response characterized by persistent maintenance of high HI titers (>8.0 log₂) up to 39 weeks post-vaccination. These findings confirm that rHVT-H9/Y280 effectively overcomes MDA interference and provides protection by inhibition of viral replication in layer chickens, making it a promising candidate for the effective control of H9N2 AIV in endemic regions. Full article

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses spread efficiently via migratory wild birds and increasingly infect mammals. The leopard cat (Prionailurus bengalensis) is an endangered mesopredator in South Korea that frequents wetland–forest ecotones and overlaps with wild waterbirds, placing it at risk of exposure. We describe a fatal HPAI H5N1 infection in a free-ranging leopard cat detected through national wildlife surveillance during a period of widespread H5N1 activity in wild birds along the East Asian–Australasian Flyway. The animal showed acute neurological and respiratory signs and died shortly after rescue. H5 viral RNA was detected by RT-qPCR in all examined tissues, with the highest load in the brain, and infectious virus was isolated from the brain, bronchoalveolar lavage fluid, and nasal swab. Pathology revealed acute serofibrinous pneumonia, severe nonsuppurative meningoencephalitis, necrotizing vasculitis with thrombosis, and necrotizing enteritis with secondary mesenteritis. Immunohistochemistry demonstrated abundant viral antigen in nasal and olfactory epithelium, olfactory bulb, neurons, endothelial cells, and bronchial and bronchiolar epithelium, supporting combined olfactory and hematogenous dissemination. This clinicopathological description expands the spectrum of HPAI-associated lesions in felids and underscores the value of wild carnivores as bioindicators of avian influenza spillover in a One Health context. Full article

The review deals with the current knowledge on the global panzootic spread of highly pathogenic avian influenza viruses (HPAIVs), with an emphasis on the H5N1 clade 2.3.4.4b virus. It describes the viral structure, replication, pathotypes and molecular determinants of host range, including sialic-acid receptor usage and key genetic mammalian-adaptation markers (PB2-E627K and PB2-D701N mutations). The host spectrum nowadays extends from wild waterfowl and poultry including seabirds, terrestrial and marine mammals and, based largely on experimental studies or molecular detection, reptiles, amphibians, and fish. Recently, the H5N1 clade 2.3.4.4b virus has shown marked tropism for lactating mammary epithelium in dairy cattle, with virions shed in raw milk. The review reports epidemiology, geographical expansion, clinical presentation, pathogenesis and pathology, diagnosis, immune responses and vaccination approaches across species. It also analyses European Union (EU) and Italian regulatory frameworks, surveillance strategies and biosecurity measures from a One-Health perspective. The review highlights how climate change, wildlife–livestock interfaces, intensive farming and global trade favor viral persistence and genomic reassortment and concludes by stressing strategic actions to limit further host adaptation and panzootic/pandemic risks. Full article

Background/Objective: The influenza virus remains one of the most prevalent respiratory pathogens, posing significant global health and economic challenges. According to the World Health Organization, the seasonal influenza virus infects up to 1 billion people and causes up to 650,000 deaths, annually. Despite influenza vaccination is the most effective available preventive strategy, its reliance on strain predictions and yearly updates limits its effectiveness. The virus’ ability to cause both epidemics and pandemics, driven by zoonotic transmissions, underscores its continuous threat. The ongoing H5N1 avian influenza outbreak is the perfect example, renewing concerns due to its ability to infect over 70 mammalian species and sporadically transmit to humans. This study aims to evaluate the protective potential of two human monoclonal antibodies against diverse and recent influenza virus strains. Method: PN-SIA28 and PN-SIA49 monoclonal antibodies were previously isolated from an individual undergoing seasonal influenza vaccination and with no known recent influenza virus exposure. Their breadth of recognition, neutralization, and conferred in vivo protection were assessed against multiple influenza viruses, including pre-pandemic strains. Structural analyses were performed to characterize antibody–antigen interactions for epitope identification. Results: Both antibodies recognize a broad range of strains and neutralize pre-pandemic avian influenza viruses, including the currently circulating H5N1 clade. Moreover, a structural analysis revealed that PN-SIA49 binds a conserved HA stem region, overlapping with epitopes recognized by other broadly neutralizing antibodies. Conclusions: These findings underscore the potential of broadly neutralizing antibodies as a basis for universal influenza countermeasures against both seasonal and pandemic threats. Additionally, they provide guidance for the design of targeted vaccine strategies to steer immune responses toward broadly protective epitopes. Full article