In vitro exposure system for study of aerosolized influenza virus.
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ABSTRACT:
SUBMITTER: Creager HM
PROVIDER: S-EPMC5221479 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAvian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies.ResultsNormal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1.ConclusionsOur findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.
| S-EPMC3439333 | biostudies-literature
Project description:Influenza viruses are presumed, but not conclusively known, to spread among humans by several possible routes. We provide evidence of a mode of transmission seldom considered for influenza: airborne virus transport on microscopic particles called "aerosolized fomites." In the guinea pig model of influenza virus transmission, we show that the airborne particulates produced by infected animals are mainly non-respiratory in origin. Surprisingly, we find that an uninfected, virus-immune guinea pig whose body is contaminated with influenza virus can transmit the virus through the air to a susceptible partner in a separate cage. We further demonstrate that aerosolized fomites can be generated from inanimate objects, such as by manually rubbing a paper tissue contaminated with influenza virus. Our data suggest that aerosolized fomites may contribute to influenza virus transmission in animal models of human influenza, if not among humans themselves, with important but understudied implications for public health.
| S-EPMC7435178 | biostudies-literature
Project description:Understanding the transmission ability of newly emerging influenza viruses is central to the development of public health preparedness and prevention strategies. Animals are used to model influenza virus infection and transmission, but the routinely used intranasal inoculation of a liquid virus suspension does not reflect natural infection. We report the development of an inoculation method that delivers an influenza virus aerosol inoculum to ferrets and the characterization of size distribution and viable virus present in aerosols shed from infected ferrets during normal breathing and sneezing. By comparing virus deposition, infectivity, virulence, and transmissibility among animals inoculated intranasally or by aerosols with a human (H3N2) or avian (H5N1) influenza virus, we demonstrate that aerosol inoculations more closely resemble a natural, airborne influenza virus infection and that viable virus is measurable in droplets and droplet nuclei exhaled by infected ferrets. These methods will provide improved risk assessment of emerging influenza viruses that pose a threat to public health.
| S-EPMC3100970 | biostudies-literature
Project description:Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus.
| S-EPMC7076363 | biostudies-literature
Project description:Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. While previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a high level of immune activation, progression to severe disease and lethality were rarely observed. Here, we evaluated a routinely used combined route of infection via intra-bronchial, oral, and intra-nasal virus inoculation with aerosolized H5N1 exposure, with or without the regular collection of bronchoalveolar lavages early after infection. Both combined route and aerosol exposure resulted in similar levels of virus replication in nose and throat and similar levels of immune activation, cytokine, and chemokine release in the blood. However, while animals exposed to H5N1 by combined-route inoculation developed severe disease with high lethality, aerosolized exposure resulted in less lesions, as measured by consecutive computed tomography and less fever and lethal disease. In conclusion, not virus levels or immune activation, but route of infection determines fatal outcome for highly pathogenic avian H5N1 influenza infection.
| S-EPMC7926951 | biostudies-literature
Project description:Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease. We reasoned that small particle aerosols of virus would penetrate the lower respiratory tract and blanket alveoli where target cells reside. We show that inhalation of aerosolized H5N1 influenza virus in cynomolgus macaques results in fulminant pneumonia that rapidly progresses to acute respiratory distress syndrome with a fatal outcome reminiscent of human disease. Molecular imaging revealed intense lung inflammation coincident with massive increases in proinflammatory proteins and IFN-? in distal airways. Aerosolized H5N1 exposure decimated alveolar macrophages, which were widely infected and caused marked influx of interstitial macrophages and neutrophils. Extensive infection of alveolar epithelial cells caused apoptosis and leakage of albumin into airways, reflecting loss of epithelial barrier function. These data establish inhalation of aerosolized virus as a critical source of exposure for fatal human infection and reveal that direct viral effects in alveoli mediate H5N1 disease. This new nonhuman primate model will advance vaccine and therapeutic approaches to prevent and treat human disease caused by highly pathogenic avian influenza viruses.
| S-EPMC5751439 | biostudies-literature
Project description:Influenza is an infectious respiratory illness caused by influenza viruses. Despite yearly updates, the efficacy of influenza vaccines is significantly curtailed by the virus antigenic drift and antigenic shift. These constant changes to the influenza virus make-up also challenge the development of a universal flu vaccine, which requires conserved antigenic regions shared by influenza viruses of different subtypes. We propose that it is possible to bypass these challenges by the development of an influenza vaccine based on conserved proteins delivered in an adjuvanted nanoparticle system. In this study, we generated influenza nanoparticle constructs using trimethyl chitosan nanoparticles (TMC nPs) as the carrier of recombinant influenza hemagglutinin subunit 2 (HA2) and nucleoprotein (NP). The purified HA2 and NP recombinant proteins were encapsulated into TMC nPs to form HA2-TMC nPs and NP-TMC nPs, respectively. Primary human intranasal epithelium cells (HNEpCs) were used as an in vitro model to measure immunity responses. HA2-TMC nPs, NP-TMC nPs, and HA2-NP-TMC nPs (influenza nanoparticle constructs) showed no toxicity in HNEpCs. The loading efficiency of HA2 and NP into the TMC nPs was 97.9% and 98.5%, respectively. HA2-TMC nPs and NP-TMC nPs more efficiently delivered HA2 and NP proteins to HNEpCs than soluble HA2 and NP proteins alone. The induction of various cytokines and chemokines was more evident in influenza nanoparticle construct-treated HNEpCs than in soluble protein-treated HNEpCs. In addition, soluble factors secreted by influenza nanoparticle construct-treated HNEpCs significantly induced MoDCs maturation markers (CD80, CD83, CD86 and HLA-DR), as compared to soluble factors secreted by protein-treated HNEpCs. HNEpCs treated with the influenza nanoparticle constructs significantly reduced influenza virus replication in an in vitro challenge assay. The results indicate that TMC nPs can be used as influenza vaccine adjuvants and carriers capable of delivering HA2 and NP proteins to HNEpCs.
| S-EPMC7410248 | biostudies-literature
Project description:Highly pathogenic avian influenza virus (HPAIV) H5N1 infections in felids have been reported in several countries. Feeding on infected birds has been suggested as potential source of infection.The study aimed to verify gastrointestinal infection as possible portal of entry for HPAIV H5N1 in cats.Four cats were infected oculo-nasopharyngeally with 10⁶ 50% egg infectious dose (EID(50) ) of HPAIV H5N1 A/cat/Germany/R606/2006. Two cats were infected intravenously with 10⁶ EID(50) and two cats were inoculated orally with 10⁷ EID(50) HPAIV embedded in gelatine capsules to mimic gastrointestinal exposure and to avoid virus contact to oropharyngeal or respiratory tissues. Cats were monitored for 6 days by physical examination, virus excretion, and peripheral blood lymphocyte counts. Blood chemical parameters (including AST, ALT, CPK, and TBIL) and viral excretion using pharyngeal and rectal swabs were analyzed.Infected cats showed elevated body temperature up to 41·3°C starting from day 1 or 2 p.i. All infected cats excreted virus in pharyngeal swabs within 2 days p.i. co-inciding with the development of clinical signs (anorexia, depression, and labored breathing) irrespective of the infection route. Virus dissemination occurred through cell-free and cell-associated viremia. Infected cats developed lymphopenia, hepatic necrosis, pneumonia, and significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), and TBIL.The experiments show that the gastrointestinal tract can serve as portal for the entry of HPAIV H5N1 into cats. Infection routes used did not influence viral tissue tropism and course of disease.
| S-EPMC4634607 | biostudies-other
Project description:COVID-19 is now a pandemic and the knowledge gap on SARS-CoV-2, i.e., the COVID-19 disease agent, dispersion persists. The US Centers for Disease Control and Prevention suggests fomites may not be the main route through which the novel coronavirus spreads. Supporting the same view, the latest the World Health Organization report recommends wearing masks for every individual in public, highlighting the transmission through the air. In the current study AERMOD, one of the most validated and tested models suggested by the USEPA, is used to model SARS-CoV-2-laden PM10 in a hypothetical outdoor environment. Multiple scenarios including particle size, wind speed, source height variations as well as and combined scenarios were modeled to estimated how exposure risk changes with the above-mentioned variables. The results reveal that wind speed majorly narrows infectious plume rather than transferring the peak concentration. The particle size variation indicated that small particles, i.e.,0.01 - 2.5 μm, could reach more than 9 m away from the source in concentration range of 10 - 20 (μg/m 3). On the other hand, source height contributes to peak plume shift rather than dispersing the infected particles. This idea was further studies by using combined scenarios which indicated height difference can impact peak plume displacement rather than wind speed. In the worst-case scenario, the results indicate that the virus-laden particles can travel outdoors more than 8 m away from an infected source. The video output of the model results clearly shows the dynamic of viral peak shifts in several scenarios. The results also indicate that in specific conditions the airborne SARS-CoV-2 can be transported to 9 m away from the source. These findings can be useful for individuals as well as decision-makers to mitigated exposure risk in real-world conditions.Supplementary informationThe online version contains supplementary material available at 10.1007/s40201-020-00602-9.
| S-EPMC7801778 | biostudies-literature
Project description:To investigate the molecular mechanisms mediating activation of human circulating MAIT cells during infection with Klebsiella pneumoniae and compare the transcriptomics with cells activated by type-I interferons or influenza virus
2023-07-07 | GSE218601 | GEO