Daved H. Fremont

Abstract Encephalitic alphaviruses, including Eastern equine encephalitis virus (EEEV), cause severe neurological disease with high mortality rates, and thus are a public health threat. Although members of the low-density lipoprotein receptor (LDLR) family, including VLDLR, LRP8 (ApoER2), and LDLR recently were identified as receptors for EEEV, residual infection in receptor-deficient cells suggests that additional entry factors exist.

Abstract Infection by yellow fever virus (YFV), the prototype Orthoflavivirus, induces a febrile syndrome in humans that can progress to liver failure, haemorrhage and death1. Despite decades of study, the entry receptors for YFV remain unclear. Here, using a surface protein-targeted CRISPR–Cas9 screen, we identified LRP4, a low-density lipoprotein receptor (LDLR) family member, as a candidate entry receptor for YFV.

Abstract The immunoregulatory metabolite itaconate accumulates in innate immune cells upon Toll-like receptor stimulation. In response to macrophage activation by lipopolysaccharide, itaconate inhibits inflammasome activation and boosts type I interferon signalling; however, the molecular mechanism of this immunoregulation remains unclear.