BackgroundSystemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether.ResultsDysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a “leaky” gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner.ConclusionsThis work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0300-8) contains supplementary material, which is available to authorized users.

In contrast to previously published reports, we have detected sustained infectivity of aerosolized influenza viruses in respiratory mucus over a wide-range of relative humidity conditions, indicating a risk of airborne transmission in a broad range of environments.

The transmission of some infectious diseases requires that pathogens can survive (i.e., remain infectious) in the environment, outside the host. Relative humidity (RH) is known to affect the survival of some microorganisms in the environment; however, the mechanism underlying the relationship has not been explained, particularly for viruses. We investigated the effects of RH on the viability of bacteria and viruses in both suspended aerosols and stationary droplets using traditional culture-based approaches. Results showed that viability of bacteria generally decreased with decreasing RH. Viruses survived well at RHs lower than 33% and at 100%, whereas their viability was reduced at intermediate RHs. We then explored the evaporation rate of droplets consisting of culture media and the resulting changes in solute concentrations over time; as water evaporates from the droplets, solutes such as sodium chloride in the media become more concentrated. Based on the results, we suggest that inactivation of bacteria is influenced by osmotic pressure resulting from elevated concentrations of salts as droplets evaporate. We propose that the inactivation of viruses is governed by the cumulative dose of solutes or the product of concentration and time, as in disinfection kinetics. These findings emphasize that evaporation kinetics play a role in modulating the survival of microorganisms in droplets.

Infectious diseases caused by enveloped viruses, such as influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), cause thousands of deaths and billions of dollars of economic losses per year. Studies have found a relationship among temperature, humidity, and influenza virus incidence, transmission, or survival; however, there are contradictory claims about whether absolute humidity (AH) or relative humidity (RH) is most important in mediating virus infectivity. Using the enveloped bacteriophage Phi6, which has been suggested as a surrogate for influenza viruses and coronaviruses, we designed a study to discern whether AH, RH, or temperature is a better predictor of virus survival in droplets. Our results show that Phi6 survived best at high (>85%) and low (<60%) RHs, with a significant decrease in infectivity at mid-range RHs (∼60 to 85%). At an AH of less than 22 g · m−3, the loss in infectivity was less than 2 orders of magnitude; however, when the AH was greater than 22 g · m−3, the loss in infectivity was typically greater than 6 orders of magnitude. At a fixed RH of 75%, infectivity was very sensitive to temperature, decreasing two orders of magnitude between 19°C and 25°C. We used random forest modeling to identify the best environmental predictors for modulating virus infectivity. The model explained 83% of variation in Phi6 infectivity and suggested that RH is the most important factor in controlling virus infectivity in droplets. This research provides novel information about the complex interplay between temperature, humidity, and the survival of viruses in droplets.IMPORTANCE Enveloped viruses are responsible for a number of infectious diseases resulting in thousands of deaths and billions of dollars of economic losses per year in the United States. There has been a lively debate in the literature over whether absolute humidity (AH) or relative humidity (RH) modulates virus infectivity. We designed a controlled study and used advanced statistical modeling techniques specifically to address this question. By providing an improved understanding of the relationship between environmental conditions and virus infectivity, our work will ultimately lead to improved strategies for predicting and controlling disease transmission.

Background: During a period of rapid growth in our understanding of the microbiology of the built environment in recent years, the majority of research has focused on bacteria and fungi. Viruses, while probably as numerous, have received less attention. In response, the Alfred P. Sloan Foundation supported a workshop entitled "Viruses in the Built Environment (VIBE)," at which experts in environmental engineering, environmental microbiology, epidemiology, infection prevention, fluid dynamics, occupational health, metagenomics, and virology convened to synthesize recent advances and identify key research questions and knowledge gaps regarding viruses in the built environment. Results: Four primary research areas and funding priorities were identified. First, a better understanding of viral communities in the built environment is needed, specifically which viruses are present and their sources, spatial and temporal dynamics, and interactions with bacteria. Second, more information is needed about viruses and health, including viral transmission in the built environment, the relationship between virus detection and exposure, and the definition of a healthy virome. The third research priority is to identify and evaluate interventions for controlling viruses and the virome in the built environment. This encompasses interactions among viruses, buildings, and occupants. Finally, to overcome the challenge of working with viruses, workshop participants emphasized that improved sampling methods, laboratory techniques, and bioinformatics approaches are needed to advance understanding of viruses in the built environment. Conclusions: We hope that identifying these key questions and knowledge gaps will engage other investigators and funding agencies to spur future research on the highly interdisciplinary topic of viruses in the built environment. There are numerous opportunities to advance knowledge, as many topics remain underexplored compared to our understanding of bacteria and fungi.

The survival of viruses in droplets is known to depend on droplets’ chemical composition, which may vary in respiratory fluid between individuals and over the course of disease. This relationship is also important for understanding the persistence of viruses in droplets generated from wastewater, freshwater, and seawater. We investigated the effects of salt (0, 1, and 35 g/L), protein (0, 100, and 1000 μg/mL), surfactant (0, 1, and 10 μg/mL), and droplet pH (4.0, 7.0, and 10.0) on the viability of viruses in 1-μL droplets pipetted onto polystyrene surfaces and exposed to 20%, 50%, and 80% relative humidity (RH) using a culture-based approach. Results showed that viability of MS2, a non-enveloped virus, was generally higher than that of Φ6, an enveloped virus, in droplets after 1 hour. The chemical composition of droplets greatly influenced virus viability. Specifically, the survival of MS2 was similar in droplets at different pH values, but the viability of Φ6 was significantly reduced in acidic and basic droplets compared to neutral ones. The presence of bovine serum albumin protected both MS2 and Φ6 from inactivation in droplets. The effects of sodium chloride and the surfactant sodium dodecyl sulfate varied by virus type and RH. Meanwhile, RH affected the viability of viruses as shown previously: viability was lowest at intermediate to high RH. The results demonstrate that the viability of viruses is determined by the chemical composition of carrier droplets, especially pH and protein content, and environmental factors. These findings emphasize the importance of understanding the chemical composition of carrier droplets in order to predict the persistence of viruses contained in them.

The phase state of respiratory aerosols and droplets has been linked to the humidity-dependent survival of pathogens such as SARS-CoV-2. To inform strategies to mitigate the spread of infectious disease, it is thus necessary to understand the humidity-dependent phase changes associated with the particles in which pathogens are suspended. Here, we study phase changes of levitated aerosols and droplets composed of model respiratory compounds (salt and protein) and growth media (organic–inorganic mixtures commonly used in studies of pathogen survival) with decreasing relative humidity (RH). Efflorescence was suppressed in many particle compositions and thus unlikely to fully account for the humidity-dependent survival of viruses. Rather, we identify organic-based, semisolid phase states that form under equilibrium conditions at intermediate RH (45 to 80%). A higher-protein content causes particles to exist in a semisolid state under a wider range of RH conditions. Diffusion and, thus, disinfection kinetics are expected to be inhibited in these semisolid states. These observations suggest that organic-based, semisolid states are an important consideration to account for the recovery of virus viability at low RH observed in previous studies. We propose a mechanism in which the semisolid phase shields pathogens from inactivation by hindering the diffusion of solutes. This suggests that the exogenous lifetime of pathogens will depend, in part, on the organic composition of the carrier respiratory particle and thus its origin in the respiratory tract. Furthermore, this work highlights the importance of accounting for spatial heterogeneities and time-dependent changes in the properties of aerosols and droplets undergoing evaporation in studies of pathogen viability.

Academic AbstractRecent studies have shown that Ebola virus can persist in wastewater, and the potential for the virus to be aerosolized and pose a risk of inhalation exposure has not been evaluated.We considered this risk for three wastewater systems: toilets, a lab-scale model of an aeration basin, and a lab-scale model of converging sewer pipes. We measured the aeroso l size distribution generated by each system, spiked Ebola virus surrogates into each system, and determined the emission rate of viruses into the air. While the number of aerosols released ranged from 10 5 to 10 7 per flush from the toilets or per minute from the lab-scale models, the total volume of aerosols generated by these systems was ~10 -8 to 10 -7 mL per flush or per minute in all cases. The Ebola virus surrogates MS2 and Phi6, spiked into toilets at an initial concentration of 10 7 PFU mL -1 , were not detected in air after flushing.Airborne concentrations of MS2 and Phi6 were ~20 PFU L -1 and ~0.1 PFU L -1 , respectively, associated with the aeration basin and sewer models. This corresponds to emission rates of 547 PFU min -1 and 3.8 PFU min -1 of MS2 and Phi6, respectively, for the aeration basin and 79 PFU min -1 and 0.3 PFU min -1 for the sewer model. Since informa tio n on the aerosolization of Ebola virus is quite limited, these emission rates can greatly help inform risk assessment of inhalation exposure to Ebola virus.iii