H1N1 Virus Infection Research Articles

Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1

BackgroundAvian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive.MethodsHerein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1).ResultsType I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection.ConclusionOur results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.

Altered gene expression in human brain microvascular endothelial cells in response to the infection of influenza H1N1 virus

Influenza viruses not only cause respiratory illness, but also have been reported to elicit neurological manifestations following acute viral infection. The central nervous system (CNS) has a specific defense mechanism against pathogens structured by cerebral microvasculature lined with brain endothelial cells to form the blood–brain barrier (BBB). To investigate the response of human brain microvascular endothelial cells (hBMECs) to the Influenza A virus (IAV), we inoculated the cells with the A/WSN/33 (H1N1) virus. We then conducted an RNAseq experiment to determine the changes in gene expression levels and the activated disease pathways following infection. The analysis revealed an effective activation of the innate immune defense by inducing the pattern recognition receptors (PRRs). Along with the production of proinflammatory cytokines, we detected an upregulation of interferons and interferon-stimulated genes, such as IFN-β/λ, ISG15, CXCL11, CXCL3 and IL-6, etc. Moreover, infected hBMECs exhibited a disruption in the cytoskeletal structure both on the transcriptomic and cytological levels. The RNAseq analysis showed different pathways and candidate genes associated with the neuroactive ligand-receptor interaction, neuroinflammation, and neurodegenerative diseases, together with a predicted activation of the neuroglia. Likewise, some genes linked with the mitochondrial structure and function displayed a significantly altered expression. En masse, this data supports that hBMECs could be infected by the IAV, which induces the innate and inflammatory immune response. The results suggest that the influenza virus infection could potentially induce a subsequent aggravation of neurological disorders.

Public Health Response to Outbreaks of Highly Pathogenic Avian Influenza (H5N1)

Abstract Aim Human infections from highly pathogenic avian influenza (HPAI) H5N1 are associated with significant morbidity and mortality internationally. This study aimed to use routinely available data to examine key strategies to prevent H5N1 transmission to humans during outbreaks in poultry in residents in Cavan, Louth, Meath and Monaghan. Study design Cross-sectional based study. Methods Data were obtained from Health Protection Team (HPT) in the Department of Public Health (DPH), HSE North-East and Department of Agriculture, Food, and the Marine (DAFM). Data entry and analyses were conducted using Microsoft Excel 2016. Results The public health response focussed on contact tracing, monitoring, and follow-up for household, farm-workers, and DAFM staff exposed on the affected farms. A total of 157 contact episodes were identified. Contacts received advice about active monitoring from their last exposure. A total of 111 (80%) were recommended chemoprophylaxis for exposure to HPAI H5N1. During the active monitoring period, two contacts developed acute respiratory symptoms, and parainfluenza 3 and rhino/enterovirus were identified in these individuals respectively. Conclusions The findings of this study, using routinely gathered data, highlighted that collaboration between public health and DAFM at regional and national level was key to rapid response to these outbreaks of HPAI in domesticated poultry. In addition, the public health response was successful in preventing H5N1 transmission from domesticated birds to humans. Key messages • HPAI H5N1 virus infections transmissions from poultry to humans is low. • Effective public health measures are crucial to further mitigate the risks to an absolute minimum.

Transcutaneous immunization via dissolving microneedles protects mice from lethal influenza H7N9 virus challenge

Avian influenza H7N9 virus has first emerged in 2013 and since then has spread in China in five seasonal waves. In humans, influenza H7N9 virus infection is associated with a high fatality rate; thus, an effective vaccine for this virus is needed. In the present study, we evaluated the usefulness of dissolving microneedles (MNs) loaded with influenza H7N9 vaccine in terms of the dissolution time, insertion capacity, insertion depth, and structural integrity of H7N9 virus in vitro. Our in vitro results showed MNs dissolved within 6 mins. The depth of skin penetration was 270 µm. After coating with a matrix material solution, the H7N9 proteins were agglomerated. We detected the H7N9 delivery time and humoral immune response in vivo. In a mouse model, the antigen retention time was longer for MNs than for intramuscular (IM) injection. The humoral response showed that similar to IM administration, MN administration increased the levels of functional and systematic antibodies and protection against the live influenza A/Anhui/01/2013 virus (Ah01/H7N9). The protection level was determined by the analysis of pathological sections of infected lungs. MN and IM administration yielded results superior to those in the control group. Taken together, these findings demonstrate that the use of dissolving MNs to deliver influenza H7N9 vaccines is a promising immunization approach.

Transcriptome analysis of pre-immune state induced by interferon gamma inhibiting the replication of H9N2 avian influenza viruses in chicken embryo fibroblasts.

Interferon (IFN), a critical antiviral cytokine produced by pathogens-induced cells, plays an important role in host innate immune system. In this study, to investigate the inhibition effect of IFN on avian influenza virus (AIV), Chicken Embryo Fibroblasts (CEFs) was infected by H9N2 AIV. The pre-immune state and transcriptome analysis have been observed and performed. The result showed chicken interferon gamma (chIFN-γ) have the most inhibitory effect on H9N2 virus among three types of chicken interferons (chIFNs). Inhibition of chIFN-γ on H9N2 virus was verified by indirect immunofluorescence, RT-qPCR and western blot. The possible signaling pathways induced by chIFN-γ with or without virus were analyzed by transcriptome. The transcriptome data were compared among H9N2-infected, chIFN-γ-treated, chIFN-γ+H9N2-treated, and Control groups. In summary, RNA-sequencing (RNA-seq) data suggested that H9N2 virus infection resulted in corresponding response of certain defensive, inflammatory and metabolism pathways to the virus replication in CEFs. Furthermore, while CEFs were treated with chIFN-γ, many immune-related signaling pathways in cells are affected and altered. Antiviral genes involved in these immune pathways such as interferon regulatory factors, chemokines, interferon-stimulated genes (ISGs) and transcription factors were significantly up-regulated, and showed significant antiviral responses. Compared with virus infected CEFs alone, pretreatment with IFN induced the expression of antiviral genes and activated related antiviral pathways, inhibited the viral replication as result. Our study provided functional annotations for antiviral genes and the basis for studying the mechanism of chIFN-γ mediated response against H9N2 AIV.

Intranasal administration of an aronia extract and carrageenan nanocomposite for the prevention of influenza A H1N1 virus infection

Intranasal administration of an aronia extract and carrageenan nanocomposite for the prevention of influenza A H1N1 virus infection

Comparison of acute respiratory distress syndrome in patients with COVID-19 and influenza A (H7N9) virus infection

ObjectivesWe aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. MethodsClinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. ResultsElevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P <0.05). The mean interval from illness onset to death was shorter in H7N9-ARDS. A total of 59.1% patients with H7N9-ARDS died of refractory hypoxemia compared with 28.9% with COVID-19-ARDS (P = 0.014). Patients with COVID-19-ARDS were more likely to die of septic shock and multiple organ dysfunction compared with H7N9-ARDS (71.2% vs 36.4%, P = 0.005). ConclusionPatients with H7N9 were more susceptible to develop severe ARDS and showed a more acute disease course. COVID-19-ARDS was associated with severe inflammatory response and coagulation dysfunction, whereas liver injury was more common in H7N9-ARDS. The main causes of death between patients with the two diseases were different.

All-trans retinoic acid increases the pathogenicity of the H9N2 influenza virus in mice

BackgroundThe H9N2 virus can infect not only birds but also humans. The pathogenicity of H9N2 virus infection is determined by an excessive immune response in the lung. All-trans retinoic acid (ATRA), the active metabolite of vitamin A, plays an important regulatory role and has been widely used in the clinical practice. This study was aimed to investigate whether ATRA could regulate the immune response to H9N2 virus infection in the lungs of mice, thereby reducing the pathogenicity of the H9N2 virus in mice.MethodsMice were infected intranasally with H9N2 virus, and injected intraperitoneally with 0.2 mL of ATRA at low (1 mg/kg), medium (5 or 10 mg/kg), or high therapeutic dose (20 mg/kg), and toxic dose (40, 60, or 80 mg/kg), once per day for 10 days. Clinical signs, survival rates, and lung gross pathology were compared between the ATRA-treated H9N2-infected group, the ATRA group, and the H9N2-infected group, to investigate the effect of different doses of ATRA on the pathogenicity of H9N2 virus. Additionally, the viral load and cytokine concentration of lungs were measured at 3, 5, 7, and 9 days after infection, to investigate the potential mechanism of ATRA in affecting the pathogenicity of the H9N2 virus. Expression levels of cellular retinoic acid-binding protein 1 (CRABP1), cellular retinoic acid-binding protein 2 (CRABP2), and Retinoic acid-inducible gene-I (RIG-I) were detected using Western blotting.ResultsThe ATRA-treated H9N2-infected mice showed more severe clinical signs compared with the H9N2-infected group. The medium and high therapeutic doses of ATRA reduced the survival rates, aggravated lung tissue damage, decreased the expression of interferon beta (IFN-β), and increased the concentrations of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and C-C motif chemokine ligand 2 (CCL2) in the lungs of the H9N2-infected mice. At the same time, the expression patterns of CRABP1, CRABP2, and RIG-I were changed in mice infected by H9N2 and treated with different concentrations of ATRA.ConclusionsOur findings suggest that the therapeutic dose of ATRA can increase the pathogenicity of the H9N2 virus. Therefore, the consequences of those infected by influenza virus would be more severe after ATRA treatment.

Cytokine Profile of Invasive Pulmonary Aspergillosis in Severe COVID-19 and Possible Therapeutic Targets.

During the SARS-CoV-2 pandemic, a higher incidence of invasive pulmonary aspergillosis was observed in patients affected by Coronavirus disease 2019 (COVID-19), leading to the delineation of a new entity named COVID-19 associated pulmonary aspergillosis (CAPA). A predisposition to invasive infection caused by Aspergillus spp. in SARS-CoV-2 infected patients can be ascribed either to the direct viral-mediated damage of the respiratory epithelium, as already observed in influenza H1N1 virus infections, or to the dysregulated immunity associated with COVID-19. This narrative review focuses on the impact of immune impairment, particularly due to cytokine dysregulation caused by Aspergillus spp. superinfection in COVID-19 for a more in-depth understanding of the molecular pathways implicated in CAPA. As immune competence has proven to be essential in protecting against CAPA onset, a role already threatened by SARS-CoV-2 infection itself, preventive strategies should focus on reducing factors that could further target the host immune system. We also aimed to focus on well-known and less-known risk factors for IPA in COVID-19 patients, related to the main causes of immune suppression, both virus-mediated and iatrogenic, including treatments currently indicated for COVID-19. Lastly, possible preventive strategies aimed at reducing morbidity and mortality due to CAPA could be implemented.

Comprehensive computational analysis reveals H5N1 influenza virus-encoded miRNAs and host-specific targets associated with antiviral immune responses and protein binding.

H5N1 virus (H5N1V) is highly contagious among birds and it was first detected in humans in 1997 during a poultry outbreak in Hong Kong. As the mechanism of its pathogenesis inside the host is still lacking, in this in-silico study we hypothesized that H5N1V might create miRNAs, which could target the genes associated with host cellular regulatory pathways, thus provide persistent refuge to the virus. Using bioinformatics approaches, several H5N1V produced putative miRNAs as well as the host genes targeted by these miRNAs were found. Functional enrichment analysis of targeted genes revealed their involvement in many biological pathways that facilitate their host pathogenesis. Eventually, the microarray dataset (GSE28166) was analyzed to validate the altered expression level of target genes and found the genes involved in protein binding and adaptive immune responses. This study presents novel miRNAs and their targeted genes, which upon experimental validation could facilitate in developing new therapeutics against H5N1V infection.

Obat Herbal dari Akar Manis (Glycyrrhiza glabra L.) untuk Pencegahan dan Pengobatan Infeksi Virus H1N1, H5N1 dan COVID-19: Systematic Review

Herbs have been used as a form of traditional medicine since ancient times. Licorice is one of the herbs that has long been used as medicine. This plant contains different plant compounds, such as glycyrrhizin, 18??glycyrrhetinic acid, glabrins A and B, and isoflavones, showing various pharmacological activities. Pharmacological experiments have shown that different extracts and pure compounds of this species exhibit broad biological properties, including antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic activities. This systematic review aims to determine the effectiveness of herbal medicine from licorice (Glycyrrhiza glabra L.) to prevent and treat H1N1, H5N1, and COVID-19 virus infections from various previous research results. This research is a systematic review using the PRISMA method. A total of 8 articles that met the inclusion and exclusion criteria were continued for analysis. A total of 8 articles discuss the effectiveness of licorice on the H1N1, H5N1, and COVID-19 viruses. The articles used include articles published in national journals and international journals. The results showed that 1) Licorice root is effectively used for the prevention and treatment of H1N1, H5N1, and COVID-19 virus infections, 2) Glycyrrhizic acid (GA) is the main compound for the development of potential anti-influenza virus agents. Overall, it can be concluded that licorice and some of its derivatives have the potential as anti-influenza agents for H1N1, H5N1, and COVID-19.

H1N1 Influenza Virus-Infected Nasal Mucosal Epithelial Progenitor Cells Promote Dendritic Cell Recruitment and Maturation

The barrier function of nasal mucosal epithelial cells plays an irreplaceable role in the spread and expansion of viruses in the body. This study found that influenza A virus H1N1 could induce apoptosis of nasal mucosal epithelial progenitor cells, cause an inflammatory response, and trigger the maturation and recruitment of nasal submucosal dendritic cells (DCs), but the mechanism remained unclear. Therefore, we used RNA sequencing and high-resolution untargeted metabolomics to sequence and perform combined bioinformatic analysis of H1N1 virus-infected nasal mucosal epithelial cells from 6 different patients. The abnormal arginine metabolism signaling pathway caused by H1N1 virus infection was screened out, and arginase inhibitors were used to interfere with the abnormal arginine metabolism and the maturation and recruitment of submucosal DCs caused by the H1N1 virus in vitro and in vivo. We conclude that H1N1 influenza virus promotes the recruitment and maturation of submucosal DCs by causing abnormal arginine metabolism in nasal mucosal epithelial cells, thereby triggering respiratory mucosal immunity.

Characterization of antibody response to an epitope spanning the haemagglutinin cleavage site of H7N9 subtype avian influenza virus for the differentiation of infected and vaccinated chickens

ABSTRACT H7N9 subtype avian influenza virus (AIV) is endemic in poultry in China, and vaccination is used as the primary strategy for disease control. However, by current serological tests, monitoring H7N9 virus infection in vaccinated poultry is difficult because vaccine-induced antibodies are not readily distinguishable from field viruses. Therefore, a test differentiating infected and vaccinated animals (DIVA) is critical for monitoring H7N9 virus. However, no DIVA test is available for the H7N9 subtype AIV. This study investigated the potential of an epitope (peptide 11) spanning the haemagglutinin (HA) cleavage site as a DIVA antigen for the H7N9 virus. The results showed that the H7N9 virus infection sera and post-challenge sera obtained from H7N9-vaccinated chickens reacted with peptide 11, whereas the sera elicited by inactivated and viral-vectored H7N9 vaccines had no reactivity with this peptide. Peptide 11 was further split into two peptides at the HA cleavage site, and the truncated peptides failed to discriminate H7N9 infected and vaccinated chickens. Peptide 11 is located in a main surface loop in the HA protein, and contains highly conserved residues in the HA cleavage site among the H7N9 subtype and different subtypes of groups 1 and 2, suggesting the potential of this peptide as a broad DIVA antigen for influenza viruses. Our study highlighted that peptide 11 is a promising DIVA antigen, and serological tests based on this peptide may serve as useful tools for monitoring H7N9 virus infection in vaccinated poultry. RESEARCH HIGHLIGHTS The epitope spanning the HA cleavage site is a potential DIVA antigen for H7N9 AIV. The epitope reacted with LP and HP H7N9 viruses. The epitope has potential as a broad DIVA antigen for influenza viruses.

Lotus (Nelumbo nucifera Gaertn.) leaf water extracts suppress influenza a viral infection via inhibition of neuraminidase and hemagglutinin

• Lotus ( Nelumbo nucifera Gaertn.) leaf inhibits influenza virus infection. • Lotus leaf directly blocks IAV binding onto the cells. • Lotus leaf suppresses neuraminidase and hemagglutinin of IAV. • Lotus leaf prevents cytopathic effect by H1N1 and H3N2 IAV. • Isoquercitrin in the lotus leaf is the main active component for an anti-IAV efficacy. Lotus ( Nelumbo nucifera Gaertn.) is a perennial aquatic plant, that has been used in folk to treat various diseases. Here, we first demonstrate the water extract of lotu s leaf (WLL) has a strong inhibitory effect on influenza A virus (IAV) infection by inhibiting neuraminidase (NA) and hemagglutinin (HA). To investigate the effect of WLL on IAV infection, we used green fluorescent protein (GFP)-tagged Influenza A/PR/8/34, fluorescence-activated cell sorting (FACS) analysis, and plaque reduction assay. WLL significantly repressed viral infection, dose-dependently. Immunofluorescence (IF) analysis confirmed that WLL reduces influenza HA, NA, M2, and NP viral proteins expression. WLL strongly inhibited HA and reduced NA activity of IAV. Among six components in WLL, isoquercitrin exerted potent antiviral efficacy. Additionally, WLL potently inhibited the cytopathic effect caused by H1N1 or H3N2 IAV. In conclusion, our results suggest that WLL could be used as a natural viral inhibitor for H1N1 and H3N2 influenza viral infection.

Characterization of H9N2 Avian Influenza Viruses Isolated from Poultry Products in a Mouse Model.

Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are not yet enzootic; however, avian influenza viruses, including H5N1, H7N9, H5N6, and H9N2, have been repeatedly detected in raw poultry meat carried by international flight passengers from Asian countries to Japan. Although H9N2 virus-contaminated poultry products intercepted by the animal quarantine service at the Japan border have been characterized in chickens and ducks, the biological properties of those H9N2 viruses in mammals remain unclear. Here, we characterized the biological features of two H9N2 virus isolates [A/chicken/Japan/AQ-HE28-50/2016 (Ck/HE28-50) and A/chicken/Japan/AQ-HE28-57/2016 (Ck/HE28-57)] in a mouse model. We found that these H9N2 viruses replicate well in the respiratory tract of infected mice without adaptation, and that Ck/HE28-57 caused body weight loss in the infected mice. Our results indicate that H9N2 avian influenza viruses isolated from raw chicken meat products illegally brought to Japan can potentially infect and cause disease in mammals.

H5N1 infection impairs the alveolar epithelial barrier through intercellular junction proteins via Itch-mediated proteasomal degradation

The H5N1 subtype of the avian influenza virus causes sporadic but fatal infections in humans. H5N1 virus infection leads to the disruption of the alveolar epithelial barrier, a pathologic change that often progresses into acute respiratory distress syndrome (ARDS) and pneumonia. The mechanisms underlying this remain poorly understood. Here we report that H5N1 viruses downregulate the expression of intercellular junction proteins (E-cadherin, occludin, claudin-1, and ZO-1) in several cell lines and the lungs of H5N1 virus-infected mice. H5N1 virus infection activates TGF-β-activated kinase 1 (TAK1), which then activates p38 and ERK to induce E3 ubiquitin ligase Itch expression and to promote occludin ubiquitination and degradation. Inhibition of the TAK1-Itch pathway restores the intercellular junction structure and function in vitro and in the lungs of H5N1 virus-infected mice. Our study suggests that H5N1 virus infection impairs the alveolar epithelial barrier by downregulating the expression of intercellular junction proteins at the posttranslational level.

Global Epidemiology of Human Infections With Variant Influenza Viruses, 1959-2021: A Descriptive Study.

Although human case numbers of variant influenza viruses have increased worldwide, the epidemiology of human cases and human-to-human transmissibility of different variant viruses remain uncertain. We used descriptive statistics to summarize the epidemiologic characteristics of variant virus infections. The hospitalization rate, case-fatality, and hospitalization-fatality risks were used to assess disease severity. Transmissibility of variant viruses between humans was determined by the effective reproductive number (Re) and probability of infection following exposure to human cases. We identified 707 naturally infected cases of variant viruses from 1959 to 2021, and their spatiotemporal/demographic characteristics changed across subtypes. The clinical severity of cases of variant viruses was generally mild; patients older than 18 years with underlying conditions were associated with hospitalization. Of 69 clusters of human infections with variant viruses (median cluster size: 2), the upper limit of Re was 0.09 (H1N1v, H1N2v, and H3N2v: 0.20 vs 0.18 vs 0.05), whereas it was not significantly different from the pooled estimates for avian influenza A(H7N9) and A(H5N1) viruses (0.10). Moreover, contacts of H5N1 cases (15.7%) had a significantly higher probability of infection than contacts of individuals with H7N9 (4.2%) and variant virus infections (4.2%-7.2%). The epidemiology of cases of variant viruses varied across time periods, geographical regions, and subtypes during 1959-2021. The transmissibility of different variant viruses between humans remains limited. However, given the continuous evolution of viruses and the rapidly evolving epidemiology of cases of variant viruses, improving the surveillance systems for human variant virus infections is needed worldwide.

Transcriptome Differences in Normal Human Bronchial Epithelial Cells in Response to Influenza A pdmH1N1 or H7N9 Virus Infection.

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus–host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.

Selenium nanoparticles inhibited H1N1 influenza virus-induced apoptosis by ROS-mediated signaling pathways.

Influenza A (H1N1) viruses are distributed around the world and pose a threat to public health. Vaccination is the main treatment strategy to prevent influenza infection, but antiviral drugs also play an important role in controlling seasonal and pandemic influenza. Currently, as influenza viruses may be developing antiviral resistance, new agents with different modes of action are being investigated. Recently, selenium nanoparticles (SeNPs), which have antiviral effects, have attracted increasing attention in biomedical interventions. The appearance of nanotechnology has attracted great attention in the field of nanomedicine. SeNPs constitute an attractive vector platform for delivering a variety of drugs to action targets. SeNPs are being explored for potential therapeutic efficacy in a variety of oxidative stress and inflammation-mediated diseases, such as cancer, arthritis, diabetes, and kidney disease. SeNPs could inhibit infection of Madin–Darby canine kidney (MDCK) cells with H1N1 and prevent chromatin condensation and DNA fragmentation. ROS play a key role in physiological processes for apoptosis. SeNPs significantly inhibited the production of reactive oxygen species (ROS) in MDCK cells. Mechanistic investigation revealed that SeNPs inhibited the apoptosis induced by H1N1 virus infection in MDCK cells by improving the level of GPx1. Our results suggest that SeNPs are an effective selenium source and a promising H1N1 influenza antiviral candidate.

Baculovirus-derived influenza virus-like particle confers complete protection against lethal H7N9 avian influenza virus challenge in chickens and mice

Currently, highly pathogenic avian influenza (HPAI) H7N9 viruses still pose a potential pandemic threat. Influenza virus-like particle (VLP) is one of the most promising vaccine strategies to complement traditional egg-dependent vaccines. Here, we generated a H7N9 VLP vaccine candidate by baculovirus expression system and evaluated its efficacy in chickens and mice. The H7N9 VLP was produced through co-infection of Sf9 insect cells with three recombinant baculoviruses expressing individual HA, NA and M1 gene of the HPAI H7N9 virus A/chicken/Guangdong/GD15/2016. Intramuscular immunization of the H7N9 VLP elicited robust antibody immune responses and conferred complete clinical protection against lethal H7N9 virus challenge both in chickens and mice. Meanwhile, H7N9 VLP significantly restrained virus shedding and dramatically alleviated pulmonary lesions caused by H7N9 virus infection in birds and mice. Interestingly, chicken antibodies induced by the H7N9 VLP also had a good cross-reactivity with H7N9 field strains isolated in different years. In addition, vaccination with the H7N9 VLP elicited high T cell immunity in mouse lung, evidenced by significantly upregulated expression of IL-2, IL-4 and IFN-γ. Furthermore, the H7N9 VLP significantly decreased the expression of some key inflammatory cytokines, such as IL6, RANTES and TNF-α in mouse lung, which may partially account for its contribution to alleviate lung pathology. Therefore, our study describes the good efficacy of the HA + NA + M1-containing H7N9 VLP both in chicken and mice models, highlighting the potential of VLP-based vaccine as a critical alternative of traditional egg-based vaccine for control of H7N9 influenza virus in both humans and poultry.