title: Epstein-Barr virus can establish infection in the absence of a classical memory B-cell population.
abstract: Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persists in the body for life after primary infection. The primary site of EBV persistence is the memory B lymphocyte, but whether the virus initially infects naïve or memory B cells is still disputed. We have analyzed EBV infection in nine cases of X-linked hyper-immunoglobulin M (hyper-IgM) syndrome who, due to a mutation in CD40 ligand gene, do not have a classical, class-switched memory B-cell population (IgD(-) CD27(+)). We found evidence of EBV infection in 67% of cases, which is similar to the infection rate found in the general United Kingdom population (60 to 70% for the relevant age range). We detected EBV DNA in peripheral blood B cells and showed in one case that the infection was restricted to the small population of nonclassical, germinal center-independent memory B cells (IgD(+) CD27(+)). Detection of EBV small RNAs, latent membrane protein 2, and EBV nuclear antigen 3C expression in peripheral blood suggests full latent viral gene expression in this population. Analysis of EBV DNA in serial samples showed variability over time, suggesting cycles of infection and loss. Our results demonstrate that short-term EBV persistence can occur in the absence of a germinal center reaction and a classical memory B-cell population.
authors.affiliation: Basic and Clinical Virology, University of Edinburgh, Royal (Dick) School of Veterinary Studies, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Conacher
authors.forename: Robin
authors.initials: R
authors.lastname: Callard
authors.forename: Karen
authors.initials: K
authors.lastname: McAulay
authors.forename: Helen
authors.initials: H
authors.lastname: Chapel
authors.forename: David
authors.initials: D
authors.lastname: Webster
authors.forename: Dinakantha
authors.initials: D
authors.lastname: Kumararatne
authors.forename: Anita
authors.initials: A
authors.lastname: Chandra
authors.forename: Gavin
authors.initials: G
authors.lastname: Spickett
authors.forename: Paul A
authors.initials: PA
authors.lastname: Hopwood
authors.forename: Dorothy H
authors.initials: DH
authors.lastname: Crawford
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000821:virology*; D007072:Immunoglobulin D / Q000032:analysis; D007075:Immunoglobulin M; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000821:virology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D020545:Respiratory Mucosa; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
chemical_list: D004279:DNA, Viral; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D012333:RNA, Messenger; D012367:RNA, Viral; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014763:Viral Matrix Proteins; D014764:Viral Proteins