Biology subjects

Prescott, J. B.

Publications and source records attributed to Prescott, J. B..

4 recordsLinked to original sources

bioRxiv2026

Elucidating genes sufficient for viral entry into cells through sequential genome-wide CRISPR activation screens

A preeminent goal of virology is to discover cellular genes that mediate virus entry. Genome-wide loss-of-function screens can illuminate single genes necessary for virus entry, but are stymied by genetic redundancy. Here we report a genome-wide CRISPR activation screening strategy to discover single genes that are sufficient for viral entry into normally-uninfectable cells. Sequential rounds of viral infection vastly enhanced screening sensitivity. This sequential screening strategy was generalizable to two unrelated viruses--Ebola and rabies viruses--and could broadly accelerate the discovery of viral entry factors.

microbiology↗

bioRxiv2025

A human arteriovenous differentiation roadmap reveals vein developmental mechanisms and vascular effects of viruses

Extracellular signals and cell-fate trajectories during vein development remain elusive, despite trailblazing insights into artery development. Here we exploit human pluripotent stem cell differentiation and mouse embryology to present a model that answers longstanding questions: vein endothelial cell (EC) differentiation unfolds in two steps driven by opposing extracellular signals. First, VEGF differentiates mesoderm into "primed" ECs, newly-defined progenitors that co-express certain arterial (SOX17) and venous (APLNR) markers. Second, primed ECs execute vein differentiation upon VEGF/ERK inhibition; however, upon VEGF activation they can instead form artery ECs. The arteriovenous plasticity of primed ECs was supported by intersectional lineage tracing. Future venous genes including NR2F2 harbor poised chromatin in primed ECs, but are only transcribed upon VEGF/ERK inhibition. SOXF transcription factors, including SOX17, confer primed ECs with vein differentiation competence. Collectively, this two-step vein differentiation model--entailing primed EC intermediates and VEGF/ERK inhibition to trigger vein differentiation--has implications for VEGF-modulating therapies.

developmental biology↗

bioRxiv2025

Egyptian rousette bat macrophages elicit divergent interferon responses and cytokine storm signalling against Marburg and Sudan viruses

Egyptian rousette bats (ERBs) are the only known natural reservoir of Marburg virus (MARV), etiologic agent of a highly-pathogenic zoonotic viral hemorrhagic fever. In ERBs, evolutionary adaptations allow for fine-tuned discrete pro-inflammatory immune responses that control MARV infection, yet permit population-level viral maintenance. To look for exclusive co-adapted responses between ERBs and MARV, we compared macrophage (M{Phi}) responses to MARV and Sudan virus (SUDV), a related filovirus not hosted by ERBs. We queried whether MARV counters normal ERB M{Phi} responses, illuminating co-adapted host responses not observed upon infection with SUDV, which fails to establish a productive infection and is efficiently immunologically cleared by ERBs. We observed stark differences in M{Phi} transcriptional responses to MARV and SUDV, including differences in Type I and III interferon (IFN)-related genes, cytokines, chemokines, cell growth and proliferation genes. We show for the first time that while MARV-infected bat M{Phi}s undergo muted IFN responses and cytokine storm signalling, SUDV induces unperturbed Type I and III IFN gene expression, stronger cytokine and chemokine responses resembling typical host responses to a foreign viral pathogen. Our findings therefore corroborate growing evidence of unique coevolutionary relationships between bats and the specific viruses they harbor.

immunology↗

bioRxiv2025

Metabolically purified human stem cell-derived hepatocytes reveal distinct effects of Ebola and Lassa viruses

Ebola and Lassa viruses require biosafety-level-4 (BSL4) containment, infect the liver, and cause deadly hemorrhagic fevers. The cellular effects of these viruses, and whether different families of hemorrhagic-fever viruses elicit similar effects, remain fundamental questions in BSL4 virology. Here, we introduce a new metabolic selection approach to create nearly-pure hepatocytes from human pluripotent stem cells, killing non-liver cells by withholding essential nutrients. Unexpectedly, Ebola and Lassa exerted starkly different effects on human hepatocytes. Ebola infection activated the integrated stress response (ISR) and WNT pathways in hepatocytes in vitro and killed them, whereas Lassa did not. Within non-human primates, Ebola likewise infected hepatocytes and activated ISR signaling in vivo. In summary, we present a single-cell transcriptional and chromatin accessibility roadmap of human hepatocyte differentiation, purification, and viral infection.

cell biology↗