Wu, J. M. | Search bioRxiv

bioRxiv2026

Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses

Langya virus is a zoonotic parahenipavirus with pandemic potential that causes acute febrile illness in people. We identified endothelial protein C receptor (EPCR) as an entry receptor for Langya, Wenzhou, and Mojiang parahenipaviruses. A 3.1 [A] cryo-electron microscopy structure reveals that Langya attachment glycoprotein engages EPCR through a site distinct from that of the ephrin binding site of Nipah G. This binding mode resembles those of protein C and a malarial adhesin, demonstrating convergent evolution. Interface substitutions abolish entry, whereas natural variation explains differential human EPCR use and predicts receptor compatibility across 26 animal species. These findings establish EPCR as a receptor for the Langya clade and provide a structural framework for understanding cross-species transmission and human infection potential.

microbiology↗

bioRxiv2022

Single nuclei RNAseq analysis of HD mouse models and human brain reveals impaired oligodendrocyte maturation and potential role for thiamine metabolism

The complexity of affected brain regions and cell types is a challenge for Huntingtons disease (HD) treatment. Here we used single nucleus RNA sequencing (snRNAseq) to investigate mechanism of pathology in the cortex and striatum from R6/2 mice at 8 and 12w and in three regions of human HD post-mortem tissue. We identified cell type-specific and cell agnostic signatures and found changes suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) were arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 were negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells showed decreased accessibility of sites regulated by OL maturation genes. Glucose and lipid metabolism were implicated in abnormal cell maturation and PRKCE and Thiamine Pyrophosphokinase 1 were identified as central genes. High dose thiamine/biotin treatment of R6/1 HD mice to target thiamine metabolism not only restored OL maturation, but also rescued pathology in neurons. These findings reveal insights into HD OL pathology that spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

neuroscience↗