[R21] Intestinal Epithelial Cellular Targets of Human Norovirus Infection

Ente: National Institute of Allergy and Infectious Diseases

Scadenza: 2028-07-31

Importo max: 240.000 EUR

Paese: US

Descrizione

PROJECT SUMMARY Human noroviruses (HuNoVs) are the leading cause of acute viral gastroenteritis worldwide, responsible for nearly 700 million infections annually, yet no vaccines or antivirals are currently available. Progress toward therapeutic development has been hindered by incomplete understanding of viral pathogenesis and historical challenges in cultivating HuNoVs ex vivo. Recent advances in human intestinal organoids (HIOs) now provide tractable systems to interrogate host–virus interactions at the cellular level. Murine studies have identified tuft cells—a rare chemosensory epithelial lineage that integrates immune and neuronal signaling—as critical targets of murine norovirus infection. Whether human tuft cells serve a similar role in HuNoV pathogenesis remains unknown. We have developed a tuft cell–enriched HIO model (~30% tuft cells, compared to <1% in vivo) via inducible expression of the lineage-specifying transcription factor POU2F3. We will utilize these modified HIOs to (1) determine whether HuNoV infects human tuft cells in tuft cell–enriched versus non-enriched HIOs, using complementary approaches including immunofluorescence, RNA in situ hybridization, and single-cell transcriptomics and (2) define the functional consequences of HuNoV infection of tuft cells, testing whether infection alters epithelial signaling, immune mediator release, or barrier function. This project is high-risk/high- reward as if tuft cells are confirmed as targets, the work will reveal an unexpected viral niche and identify new therapeutic avenues to treat HuNoV disease. Istituzione: BAYLOR COLLEGE OF MEDICINE PI: SARAH E BLUTT Progetto: 1R21AI202907-01

Settori: National Institute of Allergy and Infectious Diseases

Vai al bando originale

Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.