A randomised, open-label clinical study on the efficacy of #baloxavir marboxil and #oseltamivir for post-exposure #prevention of #influenza in a #hospital setting: a study protocol

 

Abstract

Introduction 

Healthcare settings are high-risk environments for the transmission of respiratory viruses. Effective strategies to prevent hospital-acquired influenza, particularly post-exposure prophylaxis for close contacts (CCs), are urgently needed. This study aims to assess the effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in preventing influenza virus infection among CCs who have been exposed to confirmed influenza cases and are unable to be immediately isolated in the hospital ward.

Methods and analysis 

This multicentre, randomised, open-label, parallel-controlled trial involves hospitalised patients with laboratory-confirmed influenza (index patients) and their CCs. CCs will be randomised into three groups: baloxavir marboxil, oseltamivir or placebo. Baloxavir (40 mg or 80 mg for ≥80 kg) will be administered as a single dose on day 1, while oseltamivir (75 mg) will be given once a day for 5 days. CCs will be monitored for influenza-like symptoms, with respiratory samples collected for rapid antigen test or reverse-transcription PCR testing at baseline, day 5±1 and day 10±1 or earlier if symptoms develop. The primary outcome is the 5-day incidence of clinical influenza, defined as laboratory-confirmed infection with concurrent fever and at least one respiratory symptom. Secondary outcomes will include the 5-day incidence of laboratory-confirmed influenza, the 10-day incidence of clinical influenza and the percentage of CCs infected with resistance-associated treatment-emergent influenza variants.

Ethics and dissemination 

The study has been approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2024-KY-401). The results of the study will be submitted for publication in a peer-reviewed journal with online accessibility. The full protocol, de-identified participant data and statistical code will be openly available in a public repository within 12 months after trial completion.

Trial registration number NCT06762587. 

https://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.

Source: 

Link: https://bmjopen.bmj.com/content/16/8/e118748

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Trimester-dependent vertical #transmission of #H5N1 #influenza virus through #placental and mammary routes impairs offspring development

 

Abstract

Avian influenza H5N1 has pandemic potential and historically causes more severe disease in pregnant women than the general population. With increasing transmission of H5N1 detected among placental mammals, animal models are necessary for testing countermeasures, including during pregnancy. Pregnant outbred mice infected with a contemporary strain of bovine H5N1 during the second trimester equivalent causes in utero transmission, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection results in offspring with decreased size, neurodevelopmental delays, and adolescent behavioral impairments, with infectious virus detected in the neonatal milk ring and lungs, as well as mammary tissues. H5N1 viral protein colocalizes with trophoblast cells in the placenta and epithelial cells in mammary tissue that spatially overlap with lectins for α2,3-linked SA. With the pandemic potential of H5N1, our vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

Source: 

Link: https://www.nature.com/articles/s41467-026-76891-9

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#Nipah virus #Malaysia and #Bangladesh strain-induced #pathogenesis in mice lacking type I #interferon receptor signaling

 

Abstract

Nipah virus (NiV) is a zoonotic highly pathogenic Paramyxovirus inducing lethal outbreaks of encephalitis and Acute Respiratory Distress Syndrome (ARDS) with an average case-fatality rate of 75%. Two viral strains, NiV-Malaysia (NiV-Mal) and NiV-Bangladesh (NiV-Ban), associated to distinct route of transmission, symptoms and lethality have been described. Due to the permanent threat of these emerging infections and the lack of approved therapeutics, it is crucial to improve our understanding regarding NiV-associated pathogenesis. Mice represent a small and accessible animal model, provided with numerous biological tools for the functional assessment of different genes related to antiviral response. Here, we explore the susceptibility of mice deficient for type I interferon receptor (IFNAR KO) to inoculation with either NiV-Mal or NiV-Ban through intraperitoneal or intranasal routes. Our results complement observations showing that IFNAR KO mice are susceptible to NiV-Ban infection via intraperitoneal route, although to a lesser extent than NiV-Mal, and develop encephalitis and a pulmonary syndrome with viral dissemination to various organs. Additionally, intranasal administration of both viral strains exhibited a subclinical infection with viral replication in the brain and the lungs along to the production of neutralizing antibodies in some animals. These results suggest that IFNAR KO mice may represent a reliable model permitting comparative studies of the immunopathogenesis induced by both NiV-Mal and NiV-Ban infections.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013894

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Detection of a novel #Shamonda #Orthobunyavirus in dairy #cattle, #France, June 2026

 

Abstract

In June 2026, acute fever, diarrhoea, lethargy and marked reduction of milk yield were reported in dairy cattle in eastern France. Unbiased Nanopore metagenomics on pooled plasma from affected cows detected Simbu serogroup Orthobunyavirus, provisionally named European Shamonda Virus, and recovered complete genomes. Segments L and M clustered with Nigerian Shamonda virus, whereas S showed a distinct clustering pattern, suggesting high mutation rate or reassortment. Similar findings in neighbouring countries indicate cross-border emergence requiring coordinated surveillance.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.33.2600689?emailalert=true#abstract_content

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Cardiopulmonary Failure in #Hantavirus Disease: Mechanisms, Recognition, and #ECMO-Based Management

 

Abstract

Background: 

Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. 

Methods: 

Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. 

Results: 

Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. 

Conclusions: 

HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/915

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#Treatment of #CCHF with supportive care, #favipiravir, and avatrombopag

 

Abstract

We report a severe Crimean-Congo Hemorrhagic Fever case treated with favipiravir and avatrombopag in a high-level isolation unit. This multimodal approach was associated with rapid platelet recovery, reduced transfusion requirements, and viral clearance. Combining targeted antivirals with thrombopoietin receptor agonists represents a promising strategy for managing severe CCHF coagulopathy.

Source: 

Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag415/8765585?redirectedFrom=fulltext

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Conserved #influenza A #epitope candidate regions and a benchmark of ESM-2 #sequence features

 

Abstract

Influenza A virus antigenic drift forces annual vaccine reformulation, motivating the search for conserved epitope candidates that could support broadly protective vaccines. We systematically screened influenza A virus sequences (H1N1, H3N2, H5N1; nine viral proteins) to define 98 conserved candidate regions, 38 of which were identical across the H1N1, H3N2, and H5N1 consensus sequences, all in the polymerase complex and nucleoprotein (PB2, PB1, PA, NP), whereas the ten surface-glycoprotein (HA/NA) candidates were subtype-specific. We then benchmarked two protein-language-model (ESM-2) features against alignment conservation. Group-masked log-probability correlated moderately with MSA conservation (Spearman rho = 0.25 to 0.39 for HA) but provided no incremental value for T-cell epitope discrimination (change in AUROC +0.004, p = 0.46); attention-derived contact-density was not a valid solvent-accessibility proxy. A curated antibody-epitope benchmark (22 clusters, 5 neutralization-supported) was underpowered for a high-confidence B-cell test. We document data-quality and reproducibility pitfalls (length heterogeneity, coordinate mapping, and pseudoreplication) and release the auditable benchmark. These results provide an auditable candidate resource and show that, in the evaluated benchmarks, ESM-2 sequence scores did not improve epitope prioritization beyond alignment-derived conservation.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.16.745106v1

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Of Mice and Men: #Updates on #Hantavirus Disease and #Diagnostics

 

Abstract

Hantaviruses are a diverse and widespread group of zoonotic viruses under the Orthohantavirus genus that can cause severe acute cardiopulmonary or renal disease. Hantavirus species are grouped generally as either New World or Old World based on geographic distribution, which is influenced by their respective host reservoir including rodents. Although there is no specific treatment for hantaviruses, recognizing clinical presentation and interpreting laboratory results for case identification can improve patient management. Here we review the epidemiology, clinical manifestations, and diagnostic testing options for hantavirus infection.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S1386653226000843?dgcid=rss_sd_all

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#Maraviroc Inhibits #SARS-CoV-2 Through Variant-Dependent Effects on Viral Entry and #Mpro Activity Using Single-Round Infectious Particle and Virus-like Particle Models

 

Abstract

Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC50 values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell–cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC50 = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/911

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The return of #H1N1: Reemergence of the #influenza virus A subtype H1N1 in 1977

 

Abstract

Four major influenza pandemics and two notable outbreaks have been recorded since 1900. This paper discusses the history of the 1977 influenza virus A H1N1 outbreak and re-emergence, often referred to as the “Russian flu” or the “red flu". We describe the likely events leading to the outbreak, including a brief history of the 1976 H1N1 outbreak in a military base in the United States. We reconstruct the spread of the H1N1 virus across the globe in 1977–1978 and discuss the epidemiology of the outbreak. We describe the likely origins of this unusual outbreak mainly affecting young people, including opinions and evidence pointing towards an unnatural origin. Finally, we outline the vaccines developed and vaccination campaigns that were carried out to combat the outbreak.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0264410X26007723?via%3Dihub

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A novel candidate #vaccine virus derived from #Japan's first #mammalian case of clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza virus

 

Abstract

The development of candidate vaccine viruses (CVVs) for pre-pandemic preparedness requires attenuation of pathogenicity while maintaining immunogenicity. In this study, we developed and characterized NIID-002, a reassortant virus derived from A/Ezo red fox/Hokkaido/1/2022 (H5N1; clade 2.3.4.4b), to evaluate its suitability as a candidate vaccine. NIID-002 exhibited markedly reduced pathogenicity compared with its parental strain, while retaining broad antigenic reactivity and protein yield comparable to other clade 2.3.4.4b CVVs. In mammalian models, NIID-002 demonstrated strong attenuation, causing no lethal infection in mice and only minimal weight loss with limited viral replication in ferrets. Antisera raised against NIID-002 reacted broadly with recent wild-type H5N1 isolates, suggesting potential broad protection. Protein yield analysis confirmed a production efficiency comparable to that of other CVVs within the same clade, supporting its feasibility for large-scale vaccine manufacturing. Overall, NIID-002 fulfills the key requirements for the pandemic preparedness of CVV, combining reduced pathogenicity, broad antigenic reactivity, and adequate production efficiency. These findings highlight its potential as a candidate H5N1 vaccine and underscore the continued need for surveillance and refinement of influenza vaccine strategies to address evolving viral threats.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008571?via%3Dihub

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#Community #engagement strategies for preventing recurrent #Nipah virus #outbreaks in #Bangladesh and #India: adapting a framework for outbreak preparedness and response

 

Abstract

The Nipah virus (NiV) infection is a highly fatal zoonotic disease with pandemic potential which has led to recurrent outbreaks in Bangladesh and India. While transmission pathways, including contaminated date palm sap and human-to-human spread, are increasingly identified, significant uncertainties remain. With no approved therapeutics or vaccines, prevention depends on addressing ecological and behavioural drivers of transmission. This viewpoint draws on selected evidence from NiV outbreaks and response to other zoonotic disease epidemics, such as Ebola, rabies, and the Marburg virus disease, we seek to foster discussion on why community engagement could be central to NiV prevention and preparedness. We highlight the relevance of community engagement through a spectrum of its intensity, which distinguishes between community-oriented, community-based, community-managed, and community-owned approaches. Adapting an existing model, we discuss how community engagement principles can be applied to tackle recurring NiV outbreaks in Bangladesh and India. By aligning interventions with sociocultural realities, community engagement can improve acceptability, enhance early detection, strengthen outbreak response, and support preparedness for future vaccine and therapeutic research. However, evidence specific to NiV remains limited and lessons from other diseases should be applied judiciously. In the absence of medical countermeasures, participatory, locally grounded approaches offer a sustainable pathway to reduce recurrent outbreaks and prevent future spillover events.

Source: 

Link: https://jogh.org/2026/jogh-16-03024

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Enhanced #Pathogenicity and Contact #Transmissibility of #Human-origin Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype B3.13 Compared to D1.1 in #Ferrets

 

Abstract

Since its emergence in 2020, multiple genotypes of the H5N1 clade 2.3.4.4b have been identified, with B3.13 and D1.1 emerging in the USA as two major and concerning genotypes. However, their relative pathogenicity and transmissibility in mammals have not been fully elucidated. We compared the pathogenicity and transmissibility of the first two human H5N1 clade 2.3.4.4b cases caused by B3.13 in Texas (A/Texas/37/2024; HPhTX B3.13) and D1.1 in Louisiana (A/Louisiana/12/2024; HPhLA D1.1) in a ferret model of infection and transmission. HPhTX B3.13 infection resulted in more severe clinical disease and enhanced viral shedding, with evidence of increased transmission relative to HPhLA D1.1. Histopathological analysis revealed more extensive lung pathology in animals infected with HPhTX B3.13, consistent with increased viral loads and inflammatory responses. Importantly, both genotypes showed no significant differences in reactivity to ferret sera raised against candidate vaccine virus (CVV) strains, receptor binding properties, or neuraminidase (NA) activity and thermostability. Whole-genome sequencing revealed no adaptive mutations in HPhTX B3.13 following infection or transmission. In contrast, HPhLA D1.1 showed rapid acquisition of the mammalian-adaptive mutation E627K in infected ferrets and both E627K and Q194K in the only fatal contact animal. Both mutations were associated with enhanced polymerase activity and computational analyses suggested that they enhance interactions with the mammalian host factors ANP32A and B. Our findings indicate that B3.13 is already well adapted for mammalian infection and transmission whereas D1.1 retains evolutionary potential through the rapid acquisition of adaptive mutations, highlighting important genotype-specific differences relevant to zoonotic risk assessment and pandemic preparedness.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend, Prosetta and A.A.C.T., outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has licensed some of these inventions to Medimmune, Avimex, Leinco Technologies, Castlevax, Virofend, Kerafast, Cell Signaling, EMD Millipore, Genentech, Paratus and Nura Bio, and as a result receives financial compensation. Subject to Mount Sinai receiving such financial consideration, AG-S will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy. All other authors declare no commercial or financial conflict of interest.

Funder Information Declared

NIH/NIAID, 75N93021C00014

Horizon Europe Program, KAPPA-FLU no. 101084171

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.10.744032v1

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#Lassa fever and Argentine hemorrhagic fever #treatment in guinea pigs using broad-spectrum cap-dependent #endonuclease #inhibitors

 

ABSTRACT

The class Bunyaviricetes encompasses several highly pathogenic viruses that cause lethal hemorrhagic fevers. Due to their limited prevention and treatment options and high pathogenicity, these viruses require handling in biosafety level-4 facilities. Within the bunyaviruses, arenaviruses are particularly notable for their pathogenicity and ability to cause severe hemorrhagic disease in humans. The cap-dependent endonuclease (CEN) is a unique and crucial enzyme involved in the replication cycle of these viruses. As humans do not possess a similar enzyme, CEN represents an ideal target for antiviral drug development with reduced risk of side effects. Recently, we identified a promising CEN inhibitor (CENi) demonstrating potent inhibition of virus replication. In this manuscript, we demonstrate the successful therapeutic efficacy of CENis against Lassa fever and Argentine hemorrhagic fever virus infections in guinea pig models of lethal hemorrhagic fever. In addition, we identified several CENis with antiviral activity against other highly pathogenic arenaviruses. These findings further support the potential of CENis as therapeutic agents for arenavirus infections that cause severe and often lethal hemorrhagic fever. Collectively, our results suggest that CENis are promising candidates for pan-arenavirus therapy and may also have broader utility against other CEN-containing viruses for which no approved antiviral treatments currently exist.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00880-26

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The association of empirical #treatment with #oseltamivir with the #outcome of critically ill patients admitted with severe acute respiratory illness (#SARI)

 

Abstract

Objective

Neuraminidase inhibitors (NAIs) are widely used empirically in critically ill patients with suspected influenza; however, their effect on mortality remains uncertain. This multicenter study evaluates the association between empirical treatment with oseltamivir and the outcome of critically ill patients with Severe Acute Respiratory Infection (SARI) admitted to the Intensive Care Unit (ICU).

Methods

This was a retrospective cohort study conducted in the ICUs of four hospitals in Saudi Arabia, involving adult patients with SARI from September 2012 to December 2018. Data collected were: demographics, comorbidities, clinical presentation, and outcomes among patients treated with oseltamivir and those who were not. The primary outcome was 90-day mortality. The association of oseltamivir and mortality was evaluated adjusting for propensity score.

Results

During the study period, 456 patients with SARI were included in the study, 301 were treated with empirical oseltamivir within a median of 1 day from presentation (interquartile range, 0-1 day) and a median of 4 days after symptom onset, while 155 patients were not. No significant differences were observed in baseline characteristics between the two groups. Of the included patients, 334 (73%) were tested for influenza using PCR, and 87 (26%) had a confirmed diagnosis of influenza. Patients on oseltamivir were less likely to require rescue oxygen therapy (22.9% vs. 34.8%, p=0.007), and had shorter hospital stay (20 days vs. 27 days, p=0.01). Patients treated with oseltamivir had significantly reduced 90-day mortality on adjusted analyses (aOR: 0.87, 95% CI: 0.81-0.94, p=0.0002). Subgroup analysis revealed that the association with reduced mortality extends to patients >70 years old (aOR: 0.94, 95% CI: 0.89-0.99, p=0.02) and those with negative influenza tests (aOR: 0.81, 95% CI: 0.79, 0.84, p<0.0001).

Conclusion

Among critically ill patients with SARI, empirical treatment with oseltamivir was associated with lower mortality. These results add to the body of evidence suggesting clinical benefits of oseltamivir in managing critically ill patients with influenza-like illnesses.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/20503121261478401

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High rates of #SARS-CoV-2 #reinfection in residents of long term care facilities despite robust #spike-specific #immunity following serial #vaccination

 

Abstract

Older adult residents of long-term care facilities (LTCFs) suffered high rates of mortality during the initial stages of the COVID-19 pandemic but their clinical risk has decreased markedly following vaccination. Here we determined humoral and cellular immunity following delivery of a 5th vaccine dose, an mRNA spike B1:BA.1 bivalent vaccine, to care home residents. The delivery of a 5th vaccine elicited a plateau of spike-specific immunity that remained broadly stable over 100 days in almost all people. Despite this, 15% of residents had a primary infection and 30% became reinfected during 6-months of follow up. These findings reveal that serial vaccine delivery can establish robust systemic spike-specific immune responses in frail older people but that this does not reliably prevent SARS-CoV-2 reinfection. As such, additional approaches should be considered to reduce reinfection risk in this vulnerable population group.

Source: 

Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354079

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Innate Immune Responses Induced by #H9N2 #Influenza A Virus and #Klebsiella pneumoniae Co-Infection

 

Abstract

Klebsiella pneumoniae infection following H9N2 Influenza A virus (IAV) infection causes severe pneumonia. But the underlying pathogenic mechanisms of H9N2 IAV and K. pneumoniae co-infection are complex and need to be further explored. In this study, the lung transcriptomes of mice with H9N2 IAV and K. pneumoniae co-infection were characterized by transcriptomic profiling. As a result, GO enrichment analysis revealed that the differential genes were primarily involved in the activation of immune responses, cellular components of membranes and extracellular spaces, and defense responses against pathogen infections. According to KEGG enrichment, the differentially expressed genes (DEGs) were concentrated in TLR signaling pathways, RLR signaling pathways, TNF signaling pathways and NLRP3 signaling pathways. Furthermore, in vitro cell models were established to investigate the innate immune responses induced by H9N2 IAV and K. pneumoniae CPS co-stimulation. K. pneumoniae CPS stimulation influenced the cytokine profiles of mink lung epithelial cells infected with H9N2 IAV, worsened cell viability, and aggravated apoptosis, indirectly inhibiting H9N2 IAV replication. The findings demonstrated that K. pneumoniae superinfection modulated the innate immune responses induced by H9N2 IAV infection, contributing to its pathogenesis.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/900

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