Expiratory Aerosol pH is a Driver of the Persistence of Airborne Influenza A Virus

To mitigate the spread of a viral disease, it is crucial to understand the factors that influence airborne virus transmission. However, the micro-environment to which the virus is exposed in expiratory aerosol particles is highly complex. The relative humidity, the aerosol particle size and composition, and the air composition affect virus infectivity by modulating the salt and organic concentrations within the particle, as well as the phase state. A parameter that has been overlooked is the aerosol pH. Several viruses are sensitive to acidic pH; for example, the inactivation of influenza A virus becomes very fast at pH 5.5 and below, a threshold that is quickly reached in an expiratory aerosol particle exhaled in a typical indoor environment. Therefore, aerosol acidity plays a significant role in controlling the persistence of airborne, acid-sensitive viruses such as influenza virus, and aerosol pH control could be applied to limit the risk of airborne virus transmission

Patches of Bare Ground as a Staple Commodity for Declining Ground-Foraging Insectivorous Farmland Birds

Conceived to combat widescale biodiversity erosion in farmland, agri-environment schemes have largely failed to deliver their promises despite massive financial support. While several common species have shown to react positively to existing measures, rare species have continued to decline in most European countries. Of particular concern is the status of insectivorous farmland birds that forage on the ground. We modelled the foraging habitat preferences of four declining insectivorous bird species (hoopoe, wryneck, woodlark, common redstart) inhabiting fruit tree plantations, orchards and vineyards. All species preferred foraging in habitat mosaics consisting of patches of grass and bare ground, with an optimal, species-specific bare ground coverage of 30–70% at the foraging patch scale. In the study areas, birds thrived in intensively cultivated farmland where such ground vegetation mosaics existed. Not promoted by conventional agri-environment schemes until now, patches of bare ground should be implemented throughout grassland in order to prevent further decline of insectivorous farmland birds

Expiratory Aerosol pH: The Overlooked Driver of Airborne Virus Inactivation

Respiratory viruses, including influenza virus and SARS-CoV-2, are transmitted by the airborne route. Air filtration and ventilation mechanically reduce the concentration of airborne viruses and are necessary tools for disease mitigation. However, they ignore the potential impact of the chemical environment surrounding aerosolized viruses, which determines the aerosol pH. Atmospheric aerosol gravitates toward acidic pH, and enveloped viruses are prone to inactivation at strong acidity levels. Yet, the acidity of expiratory aerosol particles and its effect on airborne virus persistence have not been examined. Here, we combine pH-dependent inactivation rates of influenza A virus (IAV) and SARS-CoV-2 with microphysical properties of respiratory fluids using a biophysical aerosol model. We find that particles exhaled into indoor air (with relative humidity ≥ 50%) become mildly acidic (pH ∼ 4), rapidly inactivating IAV within minutes, whereas SARS-CoV-2 requires days. If indoor air is enriched with nonhazardous levels of nitric acid, aerosol pH drops by up to 2 units, decreasing 99%-inactivation times for both viruses in small aerosol particles to below 30 s. Conversely, unintentional removal of volatile acids from indoor air may elevate pH and prolong airborne virus persistence. The overlooked role of aerosol acidity has profound implications for virus transmission and mitigation strategies

Inactivation mechanisms of influenza A virus under pH conditions encountered in aerosol particles as revealed by whole-virus HDX-MS

Multiple respiratory viruses, including influenza A virus (IAV), can be transmitted via expiratory aerosol particles, and aerosol pH was recently identified as a major factor influencing airborne virus infectivity. Indoors, small exhaled aerosols undergo rapid acidification to pH ~4. IAV is known to be sensitive to mildly acidic conditions encountered within host endosomes; however, it is unknown whether the same mechanisms could mediate viral inactivation within the more acidic aerosol micro-environment. Here, we identified that transient exposure to pH 4 caused IAV inactivation by a two-stage process, with an initial sharp decline in infectious titers mainly attributed to premature attainment of the post-fusion conformation of viral protein haemagglutinin (HA). Protein changes were observed by hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) as early as 10 s post-exposure to acidic conditions. Our HDX-MS data are in agreement with other more labor-intensive structural analysis techniques, such as X-ray crystallography, highlighting the ease and usefulness of whole-virus HDX-MS for multiplexed protein analyses, even within enveloped viruses such as IAV. Additionally, virion integrity was partially but irreversibly affected by acidic conditions, with a progressive unfolding of the internal matrix protein 1 (M1) that aligned with a more gradual decline in viral infectivity with time. In contrast, no acid-mediated changes to the genome or lipid envelope were detected. Improved understanding of respiratory virus fate within exhaled aerosols constitutes a global public health priority, and information gained here could aid the development of novel strategies to control the airborne persistence of seasonal and/or pandemic influenza in the future. IMPORTANCE: It is well established that COVID-19, influenza, and many other respiratory diseases can be transmitted by the inhalation of aerosolized viruses. Many studies have shown that the survival time of these airborne viruses is limited, but it remains an open question as to what drives their infectivity loss. Here, we address this question for influenza A virus by investigating structural protein changes incurred by the virus under conditions relevant to respiratory aerosol particles. From prior work, we know that expelled aerosols can become highly acidic due to equilibration with indoor room air, and our results indicate that two viral proteins are affected by these acidic conditions at multiple sites, leading to virus inactivation. Our findings suggest that the development of air treatments to quicken the speed of aerosol acidification would be a major strategy to control infectious bioburdens in the air

Evaporating 1-μl droplets exposed to 60% RH for 1 h.

<p>1-μl droplets containing inactivated influenza A virus (equivalent to 1E7 PFU/ml) exposed to 60% RH for an hour. The initial composition was the following: NaCl 8 g/l in milli-Q water (1st column); albumin 8.8 g/l + NaCl 8 g/l in milli-Q water (2nd column); transferrin 8.8 g/l + NaCl 8 g/l in milli-Q water (3rd column); casein 8.8 g/l + NaCl 8 g/l in milli-Q water (4th column); synthetic lung fluid (5th column).</p&gt

Regulation of the collagen IV network by the basement membrane protein perlecan is crucial for squamous epithelial cell morphogenesis and organ architecture

International audienceAll epithelia are surrounded by a specialized extracellular matrix, the basement membrane (BM). During development, this BM contributes to the morphogenesis of epithelial organs through different functions, the most recently added one being the shaping of the tissue. Seminal studies highlight the importance of the mechanical properties of the BM in this process. These rely on two of its core components, Collagen type IV and Perlecan, the first one supplying the BM with rigidity to constrain the tissue, the second one antagonizing this effect. Nevertheless, the number of organs that has been inspected is still scarce, and given that epithelial tissues exhibit a wide array of shapes, their forms are bound to be regulated by distinct mechanisms. This is underscored by mounting evidence that BM composition and assembly/biogenesis is tissue-specific. Moreover, previous reports have essentially focused on the mechanical role of the BM in morphogenesis at the tissue scale, but not the cell scale. Here, we took advantage of the robust conservation of core BM proteins and the limited genetic redundancy of the Drosophila model system to address how this matrix shapes a complex organ comprising a squamous, a cuboidal and a columnar epithelium. We show that Perlecan depletion affects the morphogenesis of the three epithelia, but particularly that of the squamous one, whose planar surface becomes extremely narrow. This defect is due to no other cellular function of Perlecan than its control of the squamous shape of the cells. Furthermore, we find that the lack of Perlecan modifies the structure of the Collagen type IV lattice in the BM of the squamous epithelium, and that the global reduction of Collagen type IV in the Perlecan mutant context substantially restores the morphogenesis of this epithelium. In addition, a stronger decrease in Collagen type IV exclusively in the BM of the squamous epithelium significantly rescues the organization of the two other epithelia. Our data thus sustain a model in which Perlecan counters the rigidity conveyed by Collagen type IV to the BM of the squamous epithelium through the regulation of the assembly of its scaffold, allowing the spreading of the squamous cells, spreading which is compulsory for the architecture of the whole organ