Influenza A Research Articles

Location, Age, and Antibodies Predict Avian Influenza Virus Shedding in Ring-Billed and Franklin’s Gulls in Minnesota

Influenza A virus (IAV) is a multi-host pathogen maintained in water birds and capable of spillover into humans, wildlife, and livestock. Prior research has focused on dabbling ducks as a known IAV reservoir species, yet our understanding of influenza dynamics in other water birds, including gulls, is lacking. Here, we quantify morphological and environmental drivers of serological (antibody detection by ELISA) and virological (viral RNA detection by PCR) prevalence in two gull species: ring-billed (Larus delawarensis) and Franklin’s (Leucophaeus pipixcan) gulls. Across 12 months and 10 locations, we tested over 1500 gulls for influenza viral RNA, and additionally tested antibody levels in nearly 1000 of these. We find substantial virus prevalence and a large, nonoverlapping seroprevalence, with significant differences across age and species classifications. The body condition index had minimal explanatory power to predict (sero)positivity, and the effect of the surrounding environment was idiosyncratic. Our results hint at a nontrivial relationship between virus and seropositivity, highlighting serological surveillance as a valuable counterpoint to PCR. By providing indication of both past infections and susceptibility to future infections, serosurveillance can help inform the distribution of limited resources to maximize surveillance effectiveness for a disease of high human, wildlife, and livestock concern.

Impact of organic compounds on the stability of influenza A virus in deposited 1-μL droplets.

This study investigates how the composition of respiratory fluids affects the stability of viruses in exhaled droplets. Understanding virus stability in droplets is important as it impacts how viruses spread and how we can combat them. We focus on influenza A virus (IAV) and investigate how different organic compounds found in lung fluid and nasal mucus protect the virus from inactivation. We demonstrate that the ratio of organics to salt in the fluid is an indicator of IAV stability. Among organics, small proteins are particularly effective at protecting IAV. Their effect is in part explained by the proteins' influence on the crystallization of salts in the droplets, thereby shielding the viruses from prolonged exposure to harmful salt concentrations. Understanding these mechanisms helps us grasp how viruses sustain their infectivity over time in respiratory droplets, contributing to efforts in controlling infectious diseases.

The global H5N1 influenza panzootic in mammals.

Influenza A viruses (IAV) have caused more documented global pandemics in human history than any other pathogen1,2. High pathogenicity avian influenza (HPAI) viruses belonging to the H5N1 subtype are a leading pandemic risk. Two decades after H5N1 "bird flu" became established in poultry in Southeast Asia, its descendants have resurged3, setting off an H5N1 panzootic in wild birds that is fueled by (a) rapid intercontinental spread, reaching South America and Antarctica for the first time4,5; (b) fast evolution via genomic reassortment6; and (c) frequent spillover into terrestrial7,8 and marine mammals9. The virus has sustained mammal-to-mammal transmission in multiple settings, including European fur farms10,11, South American marine mammals12-15, and US dairy cattle16-19, raising questions about whether humans are next. Historically, swine are considered optimal intermediary hosts that help avian influenza viruses (AIV) adapt to mammals before jumping to humans20. However, the altered ecology of H5N1 has opened the door to new evolutionary pathways. Could dairy cattle, farmed mink, or South American sea lions serve as new mammalian gateways to humans? Here we explore the molecular and ecological factors driving H5N1's sudden expansion in host range and assess the likelihood of different zoonotic pathways leading to an H5N1 pandemic.

Rifaximin ameliorates influenza A virus infection-induced lung barrier damage by regulating gut microbiota

Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier.Key points• Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation.• Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism.• Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.

GRP78 exerts antiviral function against influenza A virus infection by activating the IFN/JAK-STAT signaling

Influenza is an acute viral respiratory infection that causes mild to severe illness in humans and animals. Current studies show that glucose-regulated protein 78 (GRP78) can exert crucial functions during viral infection; however, the mechanism by which GRP78 regulates influenza A virus (IAV) infection remains unclear. In the present study, we found that IAV infection increased GRP78 expression. Overexpression of GRP78 significantly inhibited IAV replication, as indicated by reduced viral mRNA levels, protein levels, and viral titers. Mechanistically, Type I interferon (IFN) response signaling is upregulated during IAV infection by GRP78. Further study showed that GRP78 interacts with tyrosine kinase 2 (TYK2) and enhances its phosphorylation, thereby activating downstream STAT1/2 and antiviral IFN-stimulated gene (ISG) expression. Collectively, these results demonstrate an important mechanism by which GRP78 exerts in innate antiviral effect in IAV infection. This mechanism could be used as a therapeutic target for anti-influenza treatment.

Zinc-finger CCHC-type containing protein 8 promotes RNA virus replication by suppressing the type-I interferon responses.

Host cells have evolved an intricate regulatory network to fine tune the type-I interferon responses. However, the full picture of this regulatory network remains to be depicted. In this study, we found that knock out of zinc-finger CCHC-type containing protein 8 (ZCCHC8) impairs the replication of influenza A virus (IAV), Sendai virus (Sev), Japanese encephalitis virus (JEV), and vesicular stomatitis virus (VSV). Further investigation unveiled that ZCCHC8 suppresses the type-I interferon responses by targeting the interferon regulatory factor 3 (IRF3) signaling pathway. Mechanistically, ZCCHC8 associates with phosphorylated IRF3 and disrupts the interaction of IRF3 with the co-activator CREB-binding protein (CBP). Additionally, the direct binding of ZCCHC8 with the IFN-stimulated response element (ISRE) impairs the ISRE-binding of IRF3. Our study contributes to the comprehensive understanding for the negative regulatory network of the type-I interferon responses and provides valuable insights for the control of multiple viruses from a host-centric perspective.IMPORTANCEThe innate immune responses serve as the initial line of defense against invading pathogens and harmful substances. Negative regulation of the innate immune responses plays an essential role in avoiding auto-immune diseases and over-activated immune responses. Hence, the comprehensive understanding of the negative regulation network for innate immune responses could provide novel therapeutic insights for the control of viral infections and immune dysfunction. In this study, we report that ZCCHC8 negatively regulates the type-I interferon responses. We illustrate that ZCCHC8 impedes the IRF3-CBP association by interacting with phosphorylated IRF3 and competes with IRF3 for binding to ISRE. Our study demonstrates the role of ZCCHC8 in the replication of multiple RNA viruses and contributes to a deeper understanding of the negative regulation system for the type-I interferon responses.

A clinical protocol for a German birth cohort study of the Maturation of Immunity Against respiratory viral Infections (MIAI).

Respiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable inter-population differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive. We are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods. The results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs. https://drks.de/search/de/trial/, identifier DRKS00034278.

An effective vaccine against influenza A virus based on the matrix protein 2 (M2)

The ever-increasing antigenic diversity of the hemagglutinin (HA) of influenza A virus (IAV) poses a significant challenge for effective vaccine development. Notably, the matrix protein 2 (M2) is a highly conserved 97 amino acid long transmembrane tetrameric protein present in the envelope of IAV. More than 99 % of IAV strains circulating in American swine herds share the identical pandemic (pdm) isoform of M2, making it an ideal target antigen for a vaccine that could elicit broadly protective immunity. Here, using soluble nanoscale membrane assemblies termed nanodiscs (NDs), we designed this membrane mimetic nanostructures displaying full-length M2 in its natural transmembrane configuration (M2ND). Intramuscular (IM) immunization of swine with M2ND mixed with conventional emulsion adjuvant elicited M2-specific IgG antibodies in the serum that recognized influenza virions and M2-specific interferon-γ secreting cells present in the blood. Intranasal (IN) immunization with M2ND adjuvanted with a mycobacterial extract elicited M2-specific IgA in mucosal secretions that also recognized IAV. Immunization with an influenza whole inactivated virus (WIV) vaccine supplemented with a concurrent IM injection of M2ND mixed with an emulsion adjuvant increased the level of protective immunity afforded by the former against a challenge with an antigenically distinct H3N2 IAV, as exhibited by an enhanced elimination of virus from the lung. The lone IM administration of the M2ND vaccine mixed with an emulsion adjuvant provided measurable protection as evidenced by a >10-fold reduction or complete elimination of the challenge virus from the lung, but it did not diminish the viral load in nasal secretions nor the extent of pneumonia that ensued after the virus challenge. In contrast, an improved formulation of the M2ND vaccine that incorporated synthetic CpG oligodeoxynucleotides (CpG-ODN) in the nanostructures administered alone, via the IN and IM routes combined, provided a significant level of protective immunity against IAV as evidenced by a decreased viral load in both the upper and lower respiratory tracts and fully eliminated the occurrence of pneumonia in 89 % of the pigs immunized with this biologic. Notably, to be effective, the M2 protein must be displayed in the ND assemblies, as shown by the observation that simply mixing M2 with empty NDs incorporating CpG-ODN (eND-CpG-ODN) did not provide protective immunity. This novel M2-based vaccine offers great promise to help increase the breadth of protection afforded by conventional WIV vaccines against the diversity of IAV in circulation and, plausibly, as a broadly protective stand-alone biologic.

Red Blood Cell‐Derived Small Extracellular Vesicles Inhibit Influenza Virus through Surface‐Displayed Sialic Acids

Disrupting the conserved multivalent binding of hemagglutinin (HA) on influenza A virus (IAV) to sialic acids (SAs) on the host cell membrane offers a robust strategy to block viral attachment and infection, irrespective of antigenic evolution or drug resistance. In this study, we exploit red blood cell‐derived small extracellular vesicles (RBC sEVs) as nanodecoys by harnessing their high abundance of surface‐displayed SAs to interact with IAV through multivalent HA‐SA interactions. This high‐avidity binding inhibits viral adhesion to the cell surface, effectively preventing both attachment and infection in a dose‐dependent manner. Notably, enzymatic removal of SAs from RBC sEVs significantly diminishes their anti‐IAV efficacy. Our findings indicate that RBC sEVs possess intrinsic anti‐IAV properties due to their native multivalent SAs and hold considerable promise as antiviral therapeutics.

Red Blood Cell-Derived Small Extracellular Vesicles Inhibit Influenza Virus through Surface-Displayed Sialic Acids.

Disrupting the conserved multivalent binding of hemagglutinin (HA) on influenza A virus (IAV) to sialic acids (SAs) on the host cell membrane offers a robust strategy to block viral attachment and infection, irrespective of antigenic evolution or drug resistance. In this study, we exploit red blood cell-derived small extracellular vesicles (RBC sEVs) as nanodecoys by harnessing their high abundance of surface-displayed SAs to interact with IAV through multivalent HA-SA interactions. This high-avidity binding inhibits viral adhesion to the cell surface, effectively preventing both attachment and infection in a dose-dependent manner. Notably, enzymatic removal of SAs from RBC sEVs significantly diminishes their anti-IAV efficacy. Our findings indicate that RBC sEVs possess intrinsic anti-IAV properties due to their native multivalent SAs and hold considerable promise as antiviral therapeutics.

The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation.

E3 ubiquitin ligases are very important for regulating antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and IAV, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-β and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 presented decreased susceptibility to H9N2 and H1N1 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation of TBK1 and IRF3 and downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator that controls the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported.

Highly-Efficient Selection of Aptamers for Quantitative Fluorescence Detecting Multiple IAV Subtypes.

Influenza A virus (IAV) can cause infectious respiratory diseases in humans and animals. IAVs mutate rapidly through antigenic drift and shift, resulting in the emergence of numerous IAV subtypes and significant challenges for IAV detection. Therefore, achieving the simultaneous detection of multiple IAVs is crucial. In this work, three specific aptamers targeting the hemagglutination (HA) protein of the influenza A H5N1, H7N9, and H9N2 viruses were screened using a multichannel magnetic microfluidic chip. The aptamers exhibit nanomolar affinity and excellent specificity for the HA protein of H5N1, H7N9, and H9N2 viruses. Furthermore, three specific aptamers were truncated and labeled with different fluorescence markers to realize fluorescence quantitative detection of influenza A H5N1, H7N9, and H9N2 viruses through an aptamer sandwich assay in 1 h. The limit of detection (LOD) of the developed method is 0.38 TCID50/mL for the H5N1 virus, 0.75 TCID50/mL for the H7N9 virus, and 1.14 TCID50/mL for the H9N2 virus. The detection method has excellent specificity, strong anti-interference ability, and good reproducibility. This work provides a sensitive quantitative detection method for the H5N1, H7N9, and H9N2 viruses, enabling quantitative fluorescence detection for multiple IAV subtypes.

Aerodynamic Size-Dependent Collection and Inactivation of Virus-Laden Aerosol Particles in an Electrostatic Precipitator.

Electrostatic precipitators (ESPs) may enable high particle collection efficiency with minimal pressure drop in HVAC systems. However, studies of pathogen collection and inactivation in ESPs at medium to higher flow rates are limited. Here, a single-stage, wire-plate ESP operated at flow rates of 51 and 85 m3 h-1 was used to study the removal of virus-laden aerosol particles for three different airborne viruses: (1) bovine coronavirus (BCoV), (2) influenza A virus (IAV), and (3) porcine reproductive and respiratory virus (PRRSV). Size-resolved measurements of collection efficiency were obtained using Andersen cascade impactors (ACI) sampling upstream and downstream of the ESP. All measurements were analyzed based on three distinctive but complementary methods: (1) fluorimetry to assess physical collection, (2) RT-qPCR to assess viral RNA concentrations and (3) virus titration to assess virus viability. In general, log reductions by virus titration were highest followed by those from RT-qPCR, and last fluorimetry, suggesting that a portion of virus may be potentially inactivated in flight in the ESP. An effective migration (deposition) velocity ranging from 3.10 to 10.05 cm s-1 was also determined using the spatially resolved measurements of virus collection on the ESP plates.

Immune checkpoints are suppressed during pregnancy following influenza A virus infection.

Influenza A virus (IAV) infection is a major health risk during pregnancy. Whilst vaccination and antiviral agents are widely employed and reduce IAV-induced symptoms, they are not sufficient to control IAV infections in pregnancy, especially during pandemics. Respiratory viruses like IAV, exploit immune alterations that occur during pregnancy, including the upregulation of immune checkpoint proteins (ICPs) like PDL1, PD1 and CTLA4. We hypothesize that blocking expression of PDL1 on innate immune cells will improve maternal immunity following IAV infection. We utilized murine models of IAV infection during pregnancy with and without treatment with the immune checkpoint inhibitor (ICI), a-PDL1. Pregnant and non-pregnant mice were infected with mouse adapted IAV (A/PR/8) and assessed at 3 days post infection (3dpi). Lung cells were analyzed using flow cytometry. Lung mRNA expression of inflammatory and antiviral markers and histology was measured. Protein concentrations of inflammatory and antiviral markers, as well as viral titers was measured from lung bronchiolar lavage fluid (BALF). Lung function was also assessed. Following IAV infection, immune cells from pregnant mice had significant increases in the ICPs, PDL1, PD1 and CTLA4. a-PDL1 treatment effectively suppressed these ICPs and increased the activation marker, CD86. A-PDL1 treatment also reduced lung inflammatory cell infiltration and viral titres, increased antiviral responses, and improved lung function. Overall, IAV infection in pregnancy activates key inhibitory ICPs, leading to worsened disease outcomes. a-PDL1 treatment during IAV infection in pregnancy is an effective method to reduce ICP expression and improve overall immune cell responses.

From Viral Infections to Alzheimer's Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics.

Emerging evidence suggests that viral infections may contribute to Alzheimer's disease (AD) onset and/or progression. However, the extent of their involvement and the mechanisms through which specific viruses increase AD susceptibility risk remain elusive. We used an integrative systems bioinformatics approach to identify viral-mediated pathogenic mechanisms, by which Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A Virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could facilitate AD pathogenesis via virus-host protein-protein interactions (PPIs). We also explored potential synergistic pathogenic effects resulting from herpesvirus reactivation (HSV-1, HCMV, and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility. Herpesviridae members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-β (Aβ) formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction, they also affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress, and Aβ formation. These findings underscore the complex link between viral infections and AD development. Viruses impact AD-related processes through shared and distinct mechanisms, potentially influencing variations in AD susceptibility.

Spatially-distributed viral evolutionary analysis of Influenza A Virus (IAV)

Spatially-distributed viral evolutionary analysis of Influenza A Virus (IAV)

Detection and subtyping of influenza A virus in porcine clinical samples from Spain in 2020

A total of 1019 samples collected on 726 Spanish swine farms suffering from outbreaks of respiratory disease were screened for influenza A viruses (IAVs) using a RT-qPCR method. A subset of positive samples was further analyzed using a subtype-specific RT-qPCR method (n: 142) and Sanger sequencing (n: 64). A total of 19.4% samples from 23% farms tested positive, with infection being most common in suckling (53.6%) and weaning pigs (30.2%). Viruses belonging to four HA subtypes (H1av, H1hu, H1pdm, H3) were detected, with subtypes H1avN2, H1huN2 and H1avN1 accounting for over half of the specimens. An optimized protocol with newly designed primers allowed the detection of H3 viruses in a significant number of samples (21%). A comparison of antigenic positions revealed that circulating strains exhibited mutations with vaccine strains in a significant percentage of amino acid residues, both in the NA protein (27.8–43.3%) and particularly in the HA protein (51–75.3%).

Geniposide attenuates influenza virus-induced pneumonia by regulating inflammatory cytokines production. Evidences to elucidate the followed pathway

BackgroundInfluenza virus-induced pneumonia (IVP) is an infectious pulmonary disease characterized by exacerbated pulmonary inflammation caused by invasion of the influenza virus. IVP continues to threaten public health due to its high morbidity and mortality rates. Geniposide is one of the major bioactive constituents of G. jasminoides, which exerts antiviral and anti-inflammatory effects on influenza A virus (IAV) infection. PurposeTo investigate therapeutic effects and comprehensive mechanisms of geniposide on IAV infection and subsequent pneumonia. MethodsICR mice were infected intranasally with H1N1 (A/FM/1/47) to detect the anti-IAV activity of geniposide. Proteomics combined with function-integrated analysis were conducted to gain insight into the comprehensive mechanisms of geniposide. Subsequently, western blot was used to detect the phosphorylation of signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2), Interferon regulatory factor 9 (IRF9) and Janus kinase 1 (JAK1) in Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in lung tissue. Finally, RT-qPCR was used to detect the levels of interleukin 6 (IL-6), interleukin 17 (IL-17), interferon-γ (IFN-γ) and the STAT1 inhibitor (fludarabine) was used to verify the targeting between STAT1 and geniposide in RAW cells. ResultsGeniposide could significantly reduce the lung index, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by IAV infection. A total of 411 differentially expressed proteins were identified among control, model, and geniposide-treated group in proteomic analysis. According to function-integrated analysis, 15 KEGG pathways were enriched and divided into 9 groups (modules), including influenza A, NOD-like receptor signaling, RIG-I-like receptor signaling, and so on. Among these modules, the most intensely interacting module pair was the NOD-like receptor signaling and influenza A, in which STAT1 and STAT2 acted as hubs with critical bridgeness role in the target network of geniposide. This indicated that geniposide may mitigate inflammation and alleviate IVP by JAK/STAT signaling pathways. Moreover, validation experiments confirmed that geniposide can significantly inhibit STAT1 and STAT2 phosphorylation as well as down-regulated expression of IL-6, IFN-γ and IL-17 in lung. Furthermore, when RAW cells were treated with the STAT1 inhibitor (fludarabine), the inhibitory effect of geniposide on IFN-γ and IL-6 was attenuated significantly. ConclusionsGeniposide can attenuate IAV-induced pneumonia by regulating inflammatory cytokines production through the JAK/STAT pathway.

Clinical presentations and diagnostic approaches of pediatric necrotizing tracheobronchitis with influenza A virus and Staphylococcus aureus co-infections

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB’s clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

A comprehensive review of influenza B virus, its biological and clinical aspects.

Influenza B virus (IBV) stands as a paradox, often overshadowed by its more notorious counterpart, influenza A virus (IAV). Yet, it remains a captivating and elusive subject of scientific inquiry. Influenza B is important because it causes seasonal flu outbreaks that can lead to severe respiratory illnesses, including bronchitis, pneumonia, and exacerbations of chronic conditions like asthma. Limitations in the influenza B virus's epidemiological, immunological, and etiological evolution must be addressed promptly. This comprehensive review covers evolutionary epidemiology and pathogenesis, host-virus interactions, viral isolation and propagation, advanced molecular detection assays, vaccine composition and no animal reservoir for influenza B virus. Complex viral etiology begins with intranasal transmission of influenza B virus with the release of a segmented RNA genome that attacks host cell machinery for transcription and translation within the nucleus and the release of viral progeny. Influenza B virus prevalence in domesticated and wild canines, sea mammals, and birds is frequent, yet there is no zoonosis. The periodic circulation of influenza B virus indicates a 1-3-year cycle for monophyletic strain replacement within the Victoria strain due to frequent antigenic drift in the HA near the receptor-binding site (RBS), while the antigenic stability of Yamagata viruses portrays a more conservative evolutionary pattern. Additionally, this article outlines contemporary antiviral strategies, including pharmacological interventions and vaccination efforts. This article serves as a resource for researchers, healthcare professionals, and anyone interested in the mysterious nature of the influenza B virus. It provides valuable insights and knowledge essential for comprehending and effectively countering this viral foe, which continues to pose a significant public health threat.