Researchers have identified nectin-4 as a functional host entry receptor for rubella virus using proximity biotin labelling-based proteomics coupled with CRISPR–Cas9 validation. Rubella virus is the causative agent of rubella and congenital rubella syndrome when acquired during pregnancy. Despite the clinical importance of the virus, its cellular entry mechanisms have remained poorly characterized due to limited identification of host receptors, which has previously constrained pathogenesis research and therapeutic development.
Functional evaluation demonstrated that ectopic expression of human nectin-4 conferred susceptibility to rubella virus in non-permissive cells. Furthermore, blocking nectin-4 or genetically ablating the gene significantly reduced viral infection in host cells, establishing nectin-4 as a major entry factor for the pathogen.
At the molecular level, nectin-4 directly interacts and binds with the rubella virus envelope glycoprotein heterodimer. Following initial calcium-dependent viral attachment to cellular lipids, engagement with nectin-4 facilitates viral entry via receptor-mediated endocytosis, alongside calcium-independent viral attachment mechanisms charac...