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Chapter 24 : Epstein-Barr Virus
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Epstein-Barr virus (EBV) is a member of the Gammaherpesvirinae subfamily of the family Herpesviridae and is the prototype for the Lymphocryptovirus genus. Two types of EBV, EBV-1 and EBV-2, have been identified in most human populations. The major identified differences between the EBV-1 and EBV-2 genomes exist in the latent infection cycle nuclear antigen genes for EBV nuclear antigen 2 (EBNA-2); EBNA-LP; and EBNA-3A, -3B, and -3C and in the small, nonpolyadenylated RNA EBER-1 and -2. B lymphocytes are the primary cellular reservoir of EBV infection. The initial stage of infection involves a high-affinity interaction between the major EBV outer envelope glycoprotein, gp350, with CD21 on the surface of B cells. EBER genes are the most abundantly transcribed EBV genes in latently infected cells (104 to 105 copies/cell), distantly followed by the latent membrane protein 1 (LMP-1) gene, which, in turn, is significantly more abundant than the EBNA and LMP-2 genes. The EBV genes expressed during the late stages of lytic infection mostly encode structural viral proteins, which permit virion maintenance and egress. The viral glycoproteins are all encoded by late genes, which are of potential importance in antibody-mediated immunity to EBV. The recent demonstration that EBV can infect smooth-muscle cells in human immunodeficiency virus (HIV)-infected individuals may help explain the role of EBV in the pathogenesis of leiomyomas.
Schematic depiction of the linear EBV genome. TR, terminal repeat; IR, internal repeat. (Adapted from reference 62 with permission.)
Transcription of the EBV episome in latently infected B lymphocytes. TR, terminal repeat; IR, internal repeat. (Adapted from reference 62 with permission.)
EBV manipulates normal B-cell biology to establish a memory B-cell reservoir of infection. GC, germinal center. (Adapted from reference 114 ; copyright 2004 Massachusetts Medical Society [all rights reserved].)
Pathogenesis of EBV infection. (Adapted from reference 42 with permission of the American Society of Hematology.)
Characteristic EBV-specific antibody responses observed in young adults with AIM.
Frequency of EBV-associated posttransplant LPD