title: HLA-DQβ1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells.
abstract: Epstein-Barr virus (EBV) infects B cells and ~95% of adults are infected. EBV glycoprotein gp42 is essential for entry of virus into B cells. EBV gp42 binds to the β1 chain of HLA-DQ, -DR, and -DP on B cells, and uses these molecules for infection. To investigate if certain HLA-DQ alleles are associated with EBV seronegativity, we recruited ~3,300 healthy adult blood donors, identified 106 EBV-seronegative individuals, and randomly selected a control group of EBV-seropositive donors from the donor pool. A larger than expected proportion of EBV-seronegative subjects were HLA-DQ β1 *04/*05 and *06/*06, and to a lesser extent, *02/*03, compared with the control group, while a larger than expected portion of EBV-seropositive persons were HLA-DQ β1 *02/*02. We examined the ability of EBV gp42 to bind to different HLA-DQ molecules using human and mouse cells stably expressing these alleles. EBV gp42 bound less effectively to cells expressing HLA-DQ β1 *04/*05, *06/*06, or *03/*03 than to cells expressing HLA-DQ β1 *02/*02. These data are consistent with our observations of increased EBV seronegativity with DQ β1 *04/*05 or *06/*06 alleles. These findings emphasize the importance of a single genetic locus (HLA-DQ β1) to influence infectivity with EBV.
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases.
authors.forename: Qingxue
authors.initials: Q
authors.lastname: Li
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases.
authors.forename: Wei
authors.initials: W
authors.lastname: Bu
authors.affiliation: Division of Clinical Research, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Gabriel
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases.
authors.forename: Fiona
authors.initials: F
authors.lastname: Aguilar
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases.
authors.forename: Yo
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.|Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyadera
authors.affiliation: Immunobiology Laboratory, Department of Biomedicine, and Medical Outpatient Division, University Hospital Basel, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hess
authors.affiliation: Clinical Services Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hornung
authors.affiliation: Bioinformatics and Computational Biosciences Branch, Rocky Mountain Laboratories, NIH, Hamilton, Montana, USA.
authors.forename: Amitava
authors.initials: A
authors.lastname: Roy
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
mesh_terms: D000483:Alleles; D001402:B-Lymphocytes / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000378:metabolism*; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D014764:Viral Proteins / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: C101688:BZLF2 protein, Herpesvirus 4, Human; D006023:Glycoproteins; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D014764:Viral Proteins