Biology subjects

Schultz, E. M.

Publications and source records attributed to Schultz, E. M..

5 recordsLinked to original sources

bioRxiv2026

RSV & rhinovirus coinfection order dictates outcome via type III interferon-mediated interference in infant respiratory epithelium

Coinfection with respiratory syncytial virus (RSV) and rhinovirus (RV) is the most frequently detected coinfection in infants, yet mechanisms governing viral interference and disease outcome remain poorly understood. Although infection order is a key determinant of coinfection outcome involving RSV, influenza, rhinovirus, and SARS-CoV-2, its role in RSV/RV coinfections has not been defined. Using infant-derived human nasal organoids at air-liquid interface, we demonstrate that coinfection order fundamentally determines the outcome of RSV/RV interactions. An initial RSV infection almost completely inhibits secondary RV coinfection, whereas primary RV infection only partially impairs a subsequent RSV coinfection. These distinct outcomes are accompanied by divergent temporal antiviral and pro-inflammatory responses. Mechanistically, we identify type III interferons as a sufficient mediator of RSV-induced restriction of RV, establishing a host-driven mechanism of viral interference. In contrast, partial impairment of RSV following RV infection occurs through an interferon-independent mechanism. Despite marked differences, RSV/RV coinfections do not exacerbate epithelial injury or innate immune responses beyond that induced by RSV alone, indicating RSV is the dominant driver of pathology in coinfections. Collectively, our data establishes coinfection order as a critical determinant of RSV/RV outcome and reveals novel and mechanistic insight into critical viral-host interactions in the infant nasal epithelium.

microbiology↗

bioRxiv2026

RSV Infects the Human Nasal Epithelium via the Basolateral Route with Distinct Subgroup Infectivity and Basal Cell Tropism

Respiratory syncytial virus (RSV) causes millions of lower respiratory tract infections (LRTIs) in young children, older adults, and immunocompromised populations every year. RSV infection initiates in the upper respiratory tract and can progress to the lower airways resulting in bronchiolitis, pneumonia, and even death. RSV primarily infects epithelial cells apically, but we hypothesized that basolateral exposure of the respiratory epithelium could provide an alternative mechanism of infection that contributes to LRTI development. Using a human nose organoid-air liquid interface (HNO-ALI) model, we performed apical and basolateral inoculations with contemporaneous RSV strains (RSV/A/ON and RSV/B/BA) representing the two RSV subgroups (A and B) in both adult and infant derived HNO-ALIs. Basolateral RSV exposure resulted in delayed viral replication and apical release compared to apical infection. A statistically significant difference in basolateral infection frequency was observed between RSV/B/BA and RSV/A/ON (81.3% versus 25%). Basolateral infection selectively targeted a rare basal cell population, while preserving epithelial integrity. Using undifferentiated HNO-ALIs, we determined for the first time that Krt23+ activated basal cells (ABCs) are uniquely susceptible to RSV infection, a finding we confirmed in fully differentiated HNO-ALIs. Together, our findings show that RSV can infect the respiratory epithelium from the basolateral side by initially targeting a rare subset of basal cells before spreading apically to ciliated cells. Moreover, RSV/B/BA may have an advantage over RSV/A/ON in utilizing the basolateral infection route. These findings highlight an alternative RSV infection pathway and could be a potential mechanism for RSV spread to the lower airways. ImportanceUnderstanding the pathogenesis of RSV is essential to understanding and preventing acute and long-term sequelae from infection. The canonical understanding of RSV infection is that the virus infects and is restricted to the apical ciliated cells upon inhalation or fomite exposure. We demonstrate that an alternative route of infection - the basolateral route, can be utilized by RSV to infect the apical ciliated cells of the respiratory epithelium. We also show for the first time a novel difference in infectivity between the two contemporaneous RSV strains (RSV/A/ON and RSV/B/BA). In addition, we describe a rare basal subset-the Krt23+ activated basal cells that are uniquely susceptible to RSV thus expanding the known cellular tropism of RSV. Infection of basal cells can impact airway differentiation, homeostasis, and remodeling. Overall, our findings expand on the pathogenesis of RSV and indicate there are alternative mechanisms of infection and cell populations that are susceptible to RSV.

microbiology↗

bioRxiv2024

Pediatric human nose organoids demonstrate greater susceptibility, epithelial responses, and cytotoxicity than adults during RSV infection.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections, causing significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe as compared to healthy adults is not fully understood. In the present study, we infect both pediatric and adult human nose organoid-air liquid interface (HNO-ALIs) cell lines with two contemporary RSV isolates and demonstrate how they differ in virus replication, induction of the epithelial cytokine response, cell injury, and remodeling. Pediatric HNO-ALIs were more susceptible to early RSV replication, elicited a greater overall cytokine response, demonstrated enhanced mucous production, and manifested greater cellular damage compared to their adult counterparts. Adult HNO-ALIs displayed enhanced mucus production and robust cytokine response that was well controlled by superior regulatory cytokine response and possibly resulted in lower cellular damage than in pediatric lines. Taken together, our data suggest substantial differences in how pediatric and adult upper respiratory tract epithelium responds to RSV infection. These differences in epithelial cellular response can lead to poor mucociliary clearance and predispose infants to a worse respiratory outcome of RSV infection.

microbiology↗

bioRxiv2022

Understanding spatiotemporal effects of food supplementation on host-parasite interactions using community-based science

O_LISupplemental feeding can increase the overall health of animals but also can have variable effects on how animals defend themselves against parasites. However, the spatiotemporal effects of food supplementation on host-parasite interactions remain poorly understood, likely because large-scale, coordinated efforts are difficult. C_LIO_LIHere, we introduce the Nest Parasite Community Science Project, which is a community-based science project that coordinates studies with bird nest box "stewards" from the public and scientific community. This project was established to understand broad ecological patterns between hosts and their parasites. C_LIO_LIThe goal of this study was to determine the effect of food supplementation on eastern bluebirds (Sialia sialis) and their nest parasite community across the geographic range of the bluebirds from 2018-2021. We received 646 nests from 68 stewards in 26 states in the eastern United States. Nest box stewards reported whether or not they fed their bluebirds mealworms or suet, then followed the nesting success of the birds (number of eggs laid and hatched, percent hatched, number and percent fledged). We then identified and quantified parasites in the nests. C_LIO_LIWe found that food supplementation increased fledgling numbers and proportional fledging success. The main nest parasite taxa were parasitic blow flies (Protocalliphora sialia), but a few nests contained fleas (Ceratophyllus idius, C. gallinae, Orchopeas leucopus) and mites (Dermanyssus spp. and Ornithonyssus spp.). Blow flies were primarily found at northern latitudes, where food supplementation affected blow fly abundance. However, the direction of this effect varied substantially in direction and magnitude across years. More stewards fed bluebirds at southern latitudes than at northern latitudes, which contradicted the findings of other community-based science projects. C_LIO_LIOverall, food supplementation of birds was associated with increased host fitness but did not appear to play a consistent role in defense against these parasites across all years. Our study demonstrates the importance of coordinated studies across years and locations to understand the effects of environmental heterogeneity, including human-based food supplementation, on host-parasite dynamics. Studies during a single year or considering only a single population might not provide the necessary data to develop management strategies for species. C_LI

ecology↗

bioRxiv2019

Patterns of annual and seasonal immune investment in a temporal reproductive opportunist

Historically, investigations of how organisms investments in immunity fluctuate in response to environmental and physiological changes have focused on seasonally breeding organisms that confine reproduction to seasons with mild environmental conditions and abundant resources. Consequently, knowledge of how harsh environmental conditions and reproductive effort may interact to shape investment in immunity remains limited. The red crossbill, Loxia curvirostra, is a songbird that can breed on both short, cold and long, warm days if conifer seeds are abundant. This species provides an ideal system to investigate the influence of environmental fluctuations, reproductive investment, and their potential interactions on patterns of immune investment. In this study, we measured inter- and intra-annual immune variation in crossbills across four consecutive summers (2010-2013) and multiple seasons within one year (summer 2011-spring 2012) to explore how physiological and environmental factors impact this immune variation. Overall, the data suggest that immunity varies seasonally, among years, and in response to environmental fluctuations in food resources, precipitation, and temperature, but less in response to physiological measures such as reproduction. Collectively, this system demonstrates that a reproductively flexible organism may breed when conditions allow simultaneous investment in survival-related processes rather than at the expense of them.

ecology↗