Coreceptor restriction within the HLA-DQ locus for Epstein-Barr virus infection

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that causes infe ctious mononucleosis and is etiologically associated with malignancies of m ultiple origins. EBV enters cells through a cascade of interactions between its envelope glycoprotein gp350 and the gp42-gH-gL complex with cellular r eceptors, Membrane fusion is catalyzed by the binding of gp42, a member of the C type lectin family, to HLA class II molecule HLA-DR, -DP, or -DQ. Her e we demonstrate that only a subset of HLA-DQ alleles mediates EBV entry, i ndicating that individuals expressing these alleles may offer unique sites for EBV infection and subsequent sequelae, Additionally, the specific site within HLA-DQ determined to be essential for EBV entry is homologous to a s ite within MHC class I shown by structural studies to bind to the C type-le ctin-like natural killer receptor, providing insight into the biochemical n ature of the gp42-HLA class II interaction.