Coreceptor restriction within the HLA-DQ locus for Epstein-Barr virus infection.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that causes infectious mononucleosis and is etiologically associated with malignancies of multiple origins. EBV enters cells through a cascade of interactions between its envelope glycoprotein gp350 and the gp42-gH-gL complex with cellular receptors. 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. Here we demonstrate that only a subset of HLA-DQ alleles mediates EBV entry, indicating 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 site within MHC class I shown by structural studies to bind to the C type-lectin-like natural killer receptor, providing insight into the biochemical nature of the gp42-HLA class II interaction.
Haan
K M
KM
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Longnecker
R
R
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018698:Glutamic Acid / Q000737:chemistry; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014412:Tumor Virus Infections / Q000276:immunology*
D017931:DNA Primers; D006683:HLA-DQ Antigens; D018698:Glutamic Acid