Epstein-Barr Virus and the Human Leukocyte Antigen Complex

Purpose of Review While most adults are infected with Epstein-Barr virus (EBV), 3-5% remain uninfected. The human leukocyte antigen (HLA) complex, which controls infection by many pathogens, may influence infection and disease associated with EBV. Recent Findings Numerous EBV proteins and miRNAs downregulate HLA class I and II expression on the cell surface. HLA class II functions as a receptor for EBV entry into B cells. Specific HLA class II alleles correlate with the susceptibility of B cells to EBV infection in vitro and with EBV seropositivity or seronegativity of humans. HLA class I polymorphisms correlate with development and severity of EBV infectious mononucleosis and with the risk of several virus-associated malignancies including nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease. These findings indicate that while EBV has evolved to use MHC class II as a receptor for virus entry, polymorphisms in MHC class II, and class I influence virus infection and disease.