H1N1 Infection Research Articles

Identification of cytochrome c oxidase subunit 4 isoform 1 as a positive regulator of influenza virus replication.

Human infection with highly pathogenic H5N1 influenza virus causes severe respiratory diseases. Currently, the drugs against H5N1 are limited to virus-targeted inhibitors. However, drug resistance caused by these inhibitors is becoming a serious threat to global public health. An alternative strategy to reduce the resistance risk is to develop antiviral drugs targeting host cell proteins. In this study, we demonstrated that cytochrome c oxidase subunit 4 isoform 1 (COX41) of host cell plays an important role in H5N1 infection. Overexpression of COX41 promoted viral replication, which was inhibited by silencing or knockout the expression of COX41 in the host cell. The ribonucleoproteins (RNPs) of H5N1 were retained in the cell nucleus after knockout cellular COX41. Strikingly, inhibition of cellular COX41 by lycorine, a small-molecule compound isolated from Amaryllidaceae plants, reduced the levels of COX41-induced ROS and phosphorylation of extracellular signal-regulated kinase (ERK) in cells, thus resulting in the blockage of nuclear export of vRNP and inhibition of viral replication. In H5N1-infected mice that were treated with lycorine, we observed a reduction of viral titers and inhibition of pathological changes in the lung and trachea tissues. Importantly, no resistant virus was generated after culturing the virus with the continuous treatment of lycorine. Collectively, these findings suggest that COX41 is a positive regulator of H5N1 replication and might serve as an alternative target for anti-influenza drug development.

Age-Related Changes to the Immune System Exacerbate the Inflammatory Response to Pandemic H1N1 Infection.

Age-induced dysregulation of the immune response is a major contributor to the morbidity and mortality related to influenza a virus infections. Experimental data have shown substantial changes to the activation and maintenance of the immune response will occur with age, but it remains unclear which of these many interrelated changes are most critical to controlling the survival of the host during infection. To ascertain which mechanisms are predominantly responsible for the increased morbidity in elderly hosts, we developed an ordinary differential equation model to simulate the immune response to pandemic H1N1 infection. We fit this model to experimental data measured in young and old macaques. We determined that the severity of the infection in the elderly hosts is caused by a dysregulation in the innate immune response. We also simulated CD8+ T cell exhaustion, a common consequence of chronic and extensive infections. Our simulations indicate that while T cell exhaustion is possible in both age groups, its effects are more severe in the elderly population, as their dysregulated immune response cannot easily compensate for the exhausted T cells. Finally, we explore a therapeutic approach to reversing T cell exhaustion through an inflammatory stimulus. A controlled increase in inflammatory signals can lead to a higher chance of surviving the infection, but excess inflammation will likely lead to septic death. These results indicate that our model captures distinctions in the predominant mechanisms controlling the immune response in younger and older hosts and allows for simulations of clinically relevant therapeutic strategies post-infection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11538-022-01045-z.

Potential Threats to Human Health from Eurasian Avian-Like Swine Influenza A(H1N1) Virus and Its Reassortants.

During 2018–2020, we isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection.

Propagation of H1N1 virus through saliva movement in oesophagus: a mathematical model.

H1N1 (Swine flu) is caused by the influenza A virus which belongs to the Orthomyxoviridae family. Influenza A is very harmful to the elderly, and people with chronic respiratory disease and cardiovascular disease. Therefore, it is essential to analyse the behaviour of virus transmission through the saliva movement in oesophagus. A mathematical paradigm is developed to study the saliva movement under the applications of transverse magnetic field. Jeffrey fluid model is considered for saliva to show the viscoelastic nature. The flow nature is considered creeping and assumptions of long wavelength and low Reynolds number are adopted for analytical solutions. The Basset–Boussinesq–Oseen equation is employed to understand the propagation of H1N1 virus through saliva under the effect of applicable forces such as gravity, virtual mass, basset force, and drag forces. The suitable data for saliva, oesophagus and H1N1 virus are taken from the existing literature for simulation of the results using MATLAB software. From the graphical results, it is observed that the susceptibility to viral infections is less because the magnetic field reduces the motion of the virus particle. Further, the chances of infections in males are more as compared to females and children due to variation in viscosity of saliva. Such findings provide an understanding of the mechanics of the virus floating through the saliva (viscoelastic fluids) in the oesophagus.

Natural Reassortment of Eurasian Avian-Like Swine H1N1 and Avian H9N2 Influenza Viruses in Pigs, China.

Several zoonotic influenza A viruses detected in humans contain genes derived from avian H9N2 subtypes. We uncovered a Eurasian avian-like H1N1 swine influenza virus with polymerase basic 1 and matrix gene segments derived from the H9N2 subtype, suggesting that H9N2 viruses are infecting pigs and reassorting with swine influenza viruses in China.

Lactiplantibacillus plantarum 0111 Protects Against Influenza Virus by Modulating Intestinal Microbial-Mediated Immune Responses.

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential of Lactiplantibacillus plantarum 0111 against influenza virus H9N2. Challenge experiments showed that L. plantarum 0111 pretreatments could effectively improve mice’s survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced by L. plantarum 0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed that L. plantarum 0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration of L. plantarum 0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed that L. plantarum 0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus, L. plantarum 0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus.

Interference between avian corona and influenza viruses: The role of the epithelial architecture of the chicken trachea

Respiratory viral infections are among the major causes of disease in poultry. While viral dual infections are known to occur, viral interference in chicken airways is mechanistically hardly understood. The effects of infectious bronchitis virus (IBV) infection on tissue morphology, sialic acid (sia) expression and susceptibility of the chicken trachea for superinfection with IBV or avian influenza virus (AIV) were studied. In vivo, tracheal epithelium of chickens infected with IBV QX showed marked inflammatory cell infiltration and loss of cilia and goblet cells five days post inoculation. Plant lectin staining indicated that sialic acids redistributed from the apical membrane of the ciliated epithelium and the goblet cell cytoplasm to the basement membrane region of the epithelium. After administration of recombinant viral attachment proteins to slides of infected tissue, retained binding of AIV hemagglutinin, absence of binding of the receptor binding domain (RBD) of IBV M41 and partial reduction of IBV QX RBD were observed. Adult chicken trachea rings were used as ex vivo model to study the effects of IBV QX-induced pathological changes and receptor redistribution on secondary viral infection. AIV H9N2 infection after primary IBV infection was delayed; however, final viral loads reached similar levels as in previously uninfected trachea rings. In contrast, IBV M41 superinfection resulted in 1000-fold lower viral titers over the course of 48 h. In conclusion, epithelial changes in the chicken trachea after viral infection coincide with redistribution and likely specific downregulation of viral receptors, with the extend of subsequent viral interference dependent on viral species.

Swine influenza virus triggers ferroptosis in A549 cells to enhance virus replication

BackgroundRecently, Influenza A virus (IAV) has been shown to activate several programmed cell death pathways that play essential roles in host defense. Indeed, cell death caused by viral infection may be mediated by a mixed pattern of cell death instead of a certain single mode. Ferroptosis is a novel form of regulated cell death (RCD) that is mainly mediated by iron-dependent lipid peroxidation. Based on the proteomic data, we wondered whether IAV causes ferroptosis in host cells.MethodIn this study, a quantitative proteomics approach based on an iTRAQ combined with LC–MS/MS was used to profile proteins expressed in A549 cells infected with H1N1 swine influenza virus (SIV). Meanwhile, we measured the intracellular iron content, reactive oxygen species (ROS) release and lipid peroxidation in response to SIV infection. Finally, a drug experiment was conducted to investigate the effects of ferroptosis on modulating SIV survival.ResultsThe bioinformatics analysis revealed several proteins closely relevant to iron homeostasis and transport, and the ferroptosis signaling pathway are highly enriched in response to SIV infection. In our experiment, aberrant expression of iron-binding proteins disrupted labile iron uptake and storage after SIV infection. Meanwhile, SIV infection inhibited system the Xc−/GPX4 axis resulting in GSH depletion and the accumulation of lipid peroxidation products. Notably, cell death caused by SIV as a result of iron-dependent lipid peroxidation can be partially rescued by ferroptosis inhibitor. Additionally, blockade of the ferroptotic pathway by ferrostatin-1 (Fer-1) treatment decreased viral titers and inflammatory response.ConclusionsThis study revealed a new mode of cell death induced by IAV infection, and our findings might improve the understanding of the underlying mechanism involved in the interaction of virus and host cells.

Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network.

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6 ± 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p < .0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p < .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p = .397, p < .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.

Pathobiology of an NS1-Truncated H3N2 Swine Influenza Virus Strain in Pigs.

ABSTRACTVirus strains in the live attenuated influenza vaccine (LAIV) for swine in the United States that was on the market until 2020 encode a truncated nonstructural protein 1 of 126 amino acids (NS1del126). Their attenuation is believed to be due to an impaired ability to counteract the type I interferon (IFN)-mediated antiviral host response. However, this mechanism has been documented only in vitro for H3N2 strain A/swine/Texas/4199-2/98 NS1del126 (lvTX98), and several cases of clinical respiratory disease in the field were associated with the LAIV strains. We therefore further examined the pathobiology, including type I IFN induction, of lvTX98 in pigs and compared it with IFN induction in pig kidney-15 (PK-15) cells. lvTX98 induced up to 3-fold-higher type I IFN titers than wild-type TX98 (wtTX98) after inoculation of PK-15 cells at a high multiplicity of infection, while virus replication kinetics were similar. Mean nasal lvTX98 excretion by intranasally inoculated pigs was on average 50 times lower than that for wtTX98 but still reached titers of up to 4.3 log10 50% tissue culture infective doses/mL. After intratracheal inoculation, mean lvTX98 titers in the lower respiratory tract were significantly reduced at 18 to 48 h postinoculation (hpi) but similar to wtTX98 titers at 72 hpi. lvTX98 caused milder clinical signs than wtTX98 but induced comparable levels of microscopic and macroscopic lung lesions, peak neutrophil infiltration, and peak type I IFN. Thus, lvTX98 was partly attenuated in pigs, but this could not be associated with higher type I IFN levels.IMPORTANCE Swine influenza A viruses (swIAVs) with a truncated NS1del126 protein were strongly attenuated in previous laboratory-based safety studies and therefore approved for use as LAIVs for swine in the United States. In the field, however, the LAIV strains were detected in diagnostic samples and could regain a wild-type NS1 via reassortment with endemic swIAVs. This suggests a significant degree of LAIV replication and urges further investigation of the level and mechanism of attenuation of these LAIV strains in vivo. Here, we show that H3N2 LAIV strain lvTX98 is only partly attenuated in pigs and is excreted at significant titers after intranasal vaccination. Attenuation and restricted replication of lvTX98 in vivo seemed to be associated with the loss of NS1 functions other than type I IFN antagonism. Our findings can help to explain the occurrence of clinical respiratory disease and reassortment events associated with NS1del126-based LAIV strains in the field.

Development of amperometric biosensor based on cloned hemagglutinin gene of H1N1 (swine flu) virus.

The recent emergence of respiratory viruses especially COVID-19 and swine flu has underscored the need for robust and bedside detection methods. Swine flu virus is a very infectious virus of the respiratory system. Timely detection of this virus with high specificity and sensitivity is crucial for reducing morbidity as well as mortality. Cloning of gene segments into a non-infectious agent helps in the development of detection methods, vaccine development, and other studies. In this study, cloning was used to develop a biosensor for H1N1 pdm09 detection. A segment of the hemaglutinin gene was cloned in a vector and characterized with the help of colony touch PCR and blue–white screening. The recombinant plasmid was extracted, and the gene segment was confirmed with the help of HA-specific primers. A 5′ amine group-attached hemagglutinin (HA) gene-specific DNA probe was immobilized on the working gold electrode surface to make a quick, specific, reliable, and sensitive detection method for H1N1pdm09 virus in human nasal swab samples. The HA probe was immobilized on the cysteine applied gold electrode of the screen-printed electrode through 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Differential pulse voltammetry was performed with the help of methylene blue, which is a redox indicator for the detection of single-stranded cloned HA gene segment. The developed sensor depicted high sensitivity for the H1N1 influenza virus with a detection limit of 0.6 ng ssDNA/6 µl of the cloned HA sample. Specificity was also checked using H3N2 virus, N. meningitides, influenza A and positive H1N1pdm09 samples.

Subcellular Proteomic Analysis Reveals Dysregulation in the Organization of Human A549 Cells Infected with Influenza Virus H7N9

Background: H7N9 influenza virus poses a high risk to human beings, and proteomic evaluations of this virus may help better understand its pathogenic mechanisms in human systems. Objective: This study aimed at determining membrane proteins related to H7N9 infection. Methods: In this study, we infected primary human alveolar adenocarcinoma epithelial cells (A549) with H7N9 (including wild and mutant strains) and then produced enriched cellular membrane isolations, which were then evaluated by western blot. The proteins in these cell membrane fractions were analyzed using the isobaric Tags for Relative and Absolute Quantitation (iTRAQ) proteome technologies. Results: Differentially expressed proteins (n = 32) were identified following liquid chromatography- tandem mass spectrometry, including 20 down-regulated proteins, such as CD44 antigen and CD151 antigen, and 12 up-regulated proteins, such as tight junction protein ZO-1 and prostaglandin reductase 1. Gene Ontology database searching revealed that 20 out of the 32 differentially expressed proteins were localized to the plasma membrane. These proteins were primarily associated with the cellular component organization (n = 20) and enriched in the reactome pathway of extracellular matrix organization (n = 4). Conclusion: These findings indicate that H7N9 may dysregulate cellular organization via specific alterations to the protein profile of the plasma membrane.

Risk Prediction of Three Different Subtypes of Highly Pathogenic Avian Influenza Outbreaks in Poultry Farms: Based on Spatial Characteristics of Infected Premises in South Korea

From 2003 to 2017, highly pathogenic avian influenza (HPAI) epidemics, particularly H5N1, H5N8, and H5N6 infections in poultry farms, increased in South Korea. More recently, these subtypes of HPAI virus resurged and spread nationwide, heavily impacting the entire poultry production and supply system. Most outbreaks in poultry holdings were concentrated in the southwestern part of the country, accounting for 58.3% of the total occurrences. This geographically persistent occurrence demanded the investigation of spatial risk factors related to the HPAI outbreak and the prediction of the risk of emerging HPAI outbreaks. Therefore, we investigated 12 spatial variables for the three subtypes of HPAI virus-infected premises [(IPs), 88 H5N1, 339 H5N8, and 335 H5N6 IPs]. Then, two prediction models using statistical and machine learning algorithm approaches were built from a case-control study on HPAI H5N8 epidemic, the most prolonged outbreak, in 339 IPs and 626 non-IPs. Finally, we predicted the risk of HPAI H5N1 and H5N6 occurrence at poultry farms using a Bayesian logistic regression and machine learning algorithm model [extreme gradient boosting (XGBoost) model] built on the case-control study. Several spatial variables showed similar distribution between two subtypes of IPs, although there were distinct heterogeneous distributions of spatial variables among the three IP subtypes. The case-control study indicated that the density of domestic duck farms and the minimum distance to live bird markets were leading risk factors for HPAI outbreaks. The two prediction models showed high predictive performance for H5N1 and H5N6 occurrences [an area under the curve (AUC) of receiver operating characteristic of Bayesian model > 0.82 and XGBoost model > 0.97]. This finding emphasizes that spatial characteristics of the poultry farm play a vital role in the occurrence and forecast of HPAI outbreaks. Therefore, this finding is expected to contributing to developing prevention and control strategies.

Poly-γ-glutamic acid/Alum adjuvanted pH1N1 vaccine-immunized aged mice exhibit a significant increase in vaccine efficacy with a decrease in age-associated CD8+ T cell proportion in splenocytes

BackgroundHighly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy than young population and the age-driven decline of the influenza vaccine efficacy remains unresolved.ObjectivesThis study investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is investigated using ovalbumin as a model antigen and a commercial pandemic H1N1 (pH1N1) flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes from the vaccinated mice via single-cell transcriptome sequencing and evaluated the protective efficacy against pH1N1 virus challenge.ResultsAged mice had lower antigen trafficking and DC activation than younger mice (6-weeks), which was ameliorated by PGA/Alum with increased antigen uptake and DC activation leading to improved antigen-specific IFN-γ+CD8+ T lymphocyte frequencies higher in the vaccinated aged mice, to a similar extent as PGA/Alum adjuvanted vaccine-immunized young mice. The results of single-cell transcriptome sequencing display that PGA/Alum also reduced the proportion of age-associated CD8+ T cell subsets and gene levels of inhibitory regulators in CD8+ T cells, which may play a role in the recovery of CD8+ T cell activation. Finally, PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice were completely protected (100% survival) compared to aged mice immunized with vaccine only (0% survival) after pH1N1 virus challenge, akin to the efficacy of the vaccinated young mice (100% survival).ConclusionsPGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases of activation of DCs and effector CD8+ T cells and a decrease in age-associated CD8+ T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.

Discovery and pharmacodynamic evaluation of the novel butene lactone derivative M355 against influenza A virus in vitro and in vivo.

A new series of butene lactone derivatives were designed according to an influenza neuraminidase target and their antiviral activities against H1N1 infection of Madin-Darby canine kidney cells were evaluated. Among them, a compound that was given the name M355 was identified as the most potent against H1N1 (EC50 = 14.7 μM) with low toxicity (CC50 = 538.13 μM). It also visibly reduced the virus-induced cytopathic effect. Time-of-addition analysis indicated that H1N1 was mostly suppressed by M355 at the late stage of its infectious cycle. M355 inhibited neuraminidase in a dose-dependent fashion to a similar extent as oseltamivir, which was also indicated by a computer modeling experiment. In a mouse model, lung lesions and virus load were reduced and the expression of nucleoprotein was moderated by M355. The enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction analyses revealed that the levels of interferon-γ, interferon regulatory factor-3, Toll-like receptor-3, tumor necrosis factor-α,interleukin (IL)-1β, IL-6, and IL-8 were downregulated in the M355-treated groups, whereas the levels of IL-10 and IL-13 were upregulated. Similarly, IgG was found to be increased in infected mice plasma. These results demonstrate that M355 inhibit the expression of H1N1 in both cellular and animal models. Thus, M355 has the potential to be effective in the treatment of influenza A virus infection.

Genuine lethal infection of a wood pigeon (Columba palumbus) with high pathogenicity avian influenza H5N1, clade 2.3.4.4b, in Germany, 2022

Despite the increasing frequency of avian influenza (AI) cases in wild birds in Europe during the last decade, doves and pigeons were not recognized to be part of the AI epidemiology. Here we describe a natural, lethal HPAIV infection of subtype H5N1, clade 2.3.4.4b, in a wood pigeon (Columba palumbus) in Germany, 2022. The animal was housed in a bird sanctuary that suffered an HPAI-outbreak with multiple bird species affected. The pigeon’s post mortem findings were dominated by an acute lymphohistiocytic meningoencephalitis as well as neuronal necrosis in the grey matter of the cerebral hemispheres and in the brain stem. Influenza A viral antigen was associated to these alterations with a striking ependymal and periventricular distribution most probably indicating intraventicular liquorogenic spread of the virus. In addition, typical severe multifocal to coalescing necrotizing pancreatitis was evident. Occasionally, vascular endothelial cells showed an intense viral antigen staining. Examination of oropharyngeal and cloacal swabs and of various tissues by real-time RT-PCR corroborated systemic infection with highly pathogenic (HP) AIV of subtype H5N1. Viral loads soared in brain and pancreas samples. Full genome sequencing directly from brain tissue confirmed the assignment of the virus to clade 2.3.4.4b of the goose/Guangdong lineage bearing a polybasic hemagglutinin cleavage site. Our results demonstrate the principal susceptibility of wood pigeons to HPAIV H5N1 resulting in a sporadic infection. Considering the wide distribution and roaming of wild, feral, and racing pigeons with often close contact to humans, thorough investigation of suspected cases including pathological manifestation is advisable.

Influence of Nutritional Status and Physical Exercise on Immune Response in Metabolic Syndrome

Metabolic Syndrome (MetS) is a cluster of metabolic alterations mostly related to visceral adiposity, which in turn promotes glucose intolerance and a chronic systemic inflammatory state, characterized by immune cell infiltration. Such immune system activation increases the risk of severe disease subsequent to viral infections. Strong correlations between elevated body mass index (BMI), type-2-diabetes and increased risk of hospitalization after pandemic influenza H1N1 infection have been described. Similarly, a correlation between elevated blood glucose level and SARS-CoV-2 infection severity and mortality has been described, indicating MetS as an important predictor of clinical outcomes in patients with COVID-19. Adipose secretome, including two of the most abundant and well-studied adipokines, leptin and interleukin-6, is involved in the regulation of energy metabolism and obesity-related low-grade inflammation. Similarly, skeletal muscle hormones—called myokines—released in response to physical exercise affect both metabolic homeostasis and immune system function. Of note, several circulating hormones originate from both adipose tissue and skeletal muscle and display different functions, depending on the metabolic context. This review aims to summarize recent data in the field of exercise immunology, investigating the acute and chronic effects of exercise on myokines release and immune system function.

Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5–5.6 years old) and adult (n = 4; 47–63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.

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.

From SARS through Zika and up to Covid-19: destination recovery marketing campaigns in response to pandemics

ABSTRACT The Covid-19 pandemic has altered the paradigm of risk and recovery management but it is just one of many pandemics to have impacted destinations during the last two decades. This study examines how destination officials combated the image crises that followed SARS-2003, H1N1 Swine flu 2009–2010, Zika 2016–2017 and Covid-19 2020. The literature dealing with combating pandemics has focused on the actual management of either a specific pandemic or regional aspects of a pandemic and less on the recovery marketing and image repair aspect. As a result, tourism academic literature has a shortage of image repair theoretical frameworks addressing multi-case health-related crises. In this study, we use qualitative content analysis of news reports, websites and recovery campaigns taken from media outlets, tourism news websites, Google search engine and YouTube, over the past two decades. This paper posits a new theoretical framework: six-phase image repair strategies during pandemics.