Browsing by Author "Lin, Kaisen"
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- Aerosolization of Ebola Virus Surrogates in Wastewater SystemsLin, Kaisen (Virginia Tech, 2016-09-26)Recent 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 aerosol 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 105 to 107 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 107 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 information on the aerosolization of Ebola virus is quite limited, these emission rates can greatly help inform risk assessment of inhalation exposure to Ebola virus.
- Control of lupus nephritis by changes of gut microbiotaMu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R.; Ahmed, Sattar Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E.; Branson, David B.; Kirby, Jay L.; Goswami, Poorna; Leeth, Caroline M.; Read, Kaitlin A.; Oestreich, Kenneth J.; Vieson, Miranda D.; Reilly, Christopher M.; Luo, Xin M. (2017-07-11)Background: Systemic 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. Results: Dysbiosis 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. Conclusions: This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupusassociated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.
- Environmental Persistence of Influenza Viruses Is Dependent upon Virus Type and Host OriginKormuth, Karen A.; Lin, Kaisen; Qian, Zhihong; Myerburg, Michael M.; Marr, Linsey C.; Lakdawala, Seema S. (American Society for Microbiology, 2019-08-21)Highly transmissible influenza viruses (IV) must remain stable and infectious under a wide range of environmental conditions following release from the respiratory tract into the air. Understanding how expelled IV persist in the environment is critical to limiting the spread of these viruses. Little is known about how the stability of different IV in expelled aerosols is impacted by exposure to environmental stressors, such as relative humidity (RH). Given that not all IV are equally capable of efficient airborne transmission in people, we anticipated that not all IV would respond uniformly to ambient RH. Therefore, we have examined the stability of human-pathogenic seasonal and avian IV in suspended aerosols and stationary droplets under a range of RH conditions. H3N2 and influenza B virus (IBV) isolates are resistant to RH-dependent decay in aerosols in the presence of human airway surface liquid, but we observed strain-dependent variations in the longevities of H1N1, H3N2, and IBV in droplets. Surprisingly, low-pathogenicity avian influenza H6N1 and H9N2 viruses, which cause sporadic infections in humans but are unable to transmit person to person, demonstrated a trend toward increased sensitivity at midrange to high-range RH. Taken together, our observations suggest that the levels of vulnerability to decay at midrange RH differ with virus type and host origin.
- Influenza Virus Infectivity Is Retained in Aerosols and Droplets Independent of Relative HumidityKormuth, Karen A.; Lin, Kaisen; Prussin, Aaron J. II; Vejerano, Eric P.; Tiwari, Andrea J.; Cox, Steve S.; Myerburg, Michael M.; Lakdawala, Seema S.; Marr, Linsey C. (Oxford University Press, 2018-06-07)Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was observed in both fine aerosols and stationary droplets. Our data suggest, for the first time, that influenza viruses remain highly stable and infectious in aerosols across a wide range of relative humidities. These results have significant implications for understanding the mechanisms of transmission of influenza and its seasonality.
- Survival of MS2 and Φ6 viruses in droplets as a function of relative humidity, pH, and salt, protein, and surfactant concentrationsLin, Kaisen; Schulte, Chase R.; Marr, Linsey C. (PLOS, 2020-12-08)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.
- Survival of the Enveloped Virus Phi6 in Droplets as a Function of Relative Humidity, Absolute Humidity, and TemperaturePrussin, Aaron J. II; Schwake, David Otto; Lin, Kaisen; Gallagher, Daniel L.; Buttling, Lauren G.; Marr, Linsey C. (American Society for Microbiology, 2018-04-06)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.
- Viability of Viruses in Suspended Aerosols and Stationary Droplets as a Function of Relative Humidity and Media CompositionLin, Kaisen (Virginia Tech, 2020-05-01)The transmission of some infectious diseases requires that pathogens can survive (i.e., remain infectious) in the environment, outside the host. The viability of pathogens that are immersed in aerosols and droplets is affected by factors such as relative humidity (RH) and the chemical composition of the liquid media, but the effects of these stressors on the viability of viruses have not been extensively studied. The overall objective of this work was to investigate the effects of RH and media composition on the viability of viruses in suspended aerosols and stationary droplets. We used a custom rotating drum to study the viability of airborne 2009 pandemic influenza A(H1N1) virus across a wide range of RHs. Viruses in culture medium supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all RH levels tested. We further investigated the viability of two model viruses, MS2 and Φ6, in suspended aerosols and stationary droplets consisting of culture media. Contrary to the results for influenza virus, we observed a U-shaped viability pattern against RH, where viruses retained their viability at low and extreme high RHs, but decayed significantly at intermediate to high RHs. By characterizing the droplet evaporation kinetics, we demonstrated that RH mediated the evaporation rate of droplets, induced changes in solute concentrations, and modulated the cumulative dose of solutes to which viruses were exposed as droplets evaporated. We proposed that the decay of viruses in droplets follows disinfection kinetics. Lastly, we manipulated the chemical composition of media to explore the stability of viruses as a function of pH and salt, protein, and surfactant concentrations. Results suggested that the effects of salt and surfactant were RH and strain-dependent. Acidic and basic media effectively inactivated enveloped virus. Protein had protective effect on both non-enveloped and enveloped viruses. Results from this work has advanced the understanding of virus viability in the environment and has significant implications for understanding infectious disease transmission.
- Viruses in the Built Environment (VIBE) meeting reportPrussin, Aaron J. II; Belser, Jessica A.; Bischoff, Werner; Kelley, Scott T.; Lin, Kaisen; Lindsley, William G.; Nshimyimana, Jean P.; Schuit, Michael; Wu, Zhenyu; Bibby, Kyle J.; Marr, Linsey C. (2020-01-04)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. Video abstract.