Biology subjects

Cooley, K. A.

Publications and source records attributed to Cooley, K. A..

2 recordsLinked to original sources

bioRxiv2025

Humoral correlates of protection in a mouse model of echovirus infection

Echoviruses commonly infect humans and can cause severe outcomes, including meningitis and liver failure, especially in neonates and immunocompromised individuals. Although recent progress has been made in understanding acute pathogenesis and innate immunity to echoviruses, adaptive immune responses remain poorly defined, in part due to the lack of an appropriate small animal model of infection. Here, we developed a translational mouse model of echovirus infection using hFc mice, which express human FcRn, the echovirus receptor, while maintaining functional IgG circulation. Primary echovirus infection caused acute disease and elicited virus-specific nAbs, IgG, and IgM only in hFc mice, which express human FcRn and support IgG transport, but not in parental Tg32 mice that lack IgG transport. These humoral responses correlated with protection against a homologous lethal-dose challenge. The protective role of these antibodies was confirmed by passive transfer of immune serum, which conferred complete, sterilizing protection. Statistical modeling identified E5-specific nAb, total IgG, and IgG1 titers as the strongest predictors of survival following infection, identifying novel correlates of protection. These findings establish hFc mice as a robust translational model for dissecting echovirus adaptive immunity, define the humoral response to infection, and identify correlates of protection to guide future vaccine development and preclinical evaluation.

immunology↗

bioRxiv2024

Interferon Epsilon Protects Epithelial Barriers from Viral Infection through Autocrine Intracellular Signaling

Antiviral defenses at mucosal barriers are essential for preventing viral entry and systemic infection. Interferon epsilon (IFN{varepsilon}) is a unique type I IFN that, unlike other family members, is not induced by infection but is constitutively expressed in epithelial tissues. IFN{varepsilon} was initially characterized in the female reproductive tract (FRT), where it provides broad antiviral protection, but its roles outside the FRT remain poorly defined. Here, we used Ifn{varepsilon}-/- mice and single-cell RNA sequencing to delineate IFN{varepsilon} function across distinct mucosal surfaces. In the FRT, Ifn{varepsilon} expression was restricted to specific epithelial subsets, was independent of estrous stage, and maintained basal ISG expression. IFN{varepsilon} was also retained intracellularly in primary human FRT-derived cells. Extending these analyses to the intestine, we found that IFN{varepsilon} is highly expressed in villous-tip enterocytes of the small intestine in vivo, where it sustains inflammatory enterocyte subsets and maintains type III IFN expression. Loss of Ifn{varepsilon} depleted these subsets and rendered mice more susceptible to enteric viral infection. Together, these findings establish IFN{varepsilon} as a constitutively expressed, spatially restricted IFN that coordinates mucosal antiviral defenses across both reproductive and gastrointestinal epithelial tissues.

immunology↗