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Epstein–Barr Virus: Pathogenesis and Host Immune Response

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Viruses and Human Cancer

Abstract

Epstein–Barr virus (EBV) is a human gamma-herpesvirus with a large double-stranded DNA genome (168–184 kbp) that encodes for nearly 100 genes. There are two closely related EBV subtypes, EBV-1 and EBV-2, which differ in genetic sequence, biological properties, and geographical distribution. The viral genome is composed of two terminal repeat units, five unique regions, and four internal repeat units. The genes can be broadly divided into latent genes and lytic genes. Latent genes ensure virus persistence in infected cells by maintaining virus copy number, inhibiting immune recognition, blocking apoptosis, and providing tonic growth signals to infected cells. Lytic genes are responsible for virus production, by switching on the replication program, blocking apoptosis, inhibiting immune recognition, activating infected cells, and producing virion structural components. The mature enveloped virion is composed of a dense DNA core, icosahedral capsid, amorphous tegument protein, and a phospholipid envelope. EBV infection is transmitted from human to human through saliva. After a brief phase of lytic infection within oral epithelium, EBV infects naïve tonsillar B cells by binding of the EBV envelope glycoprotein gp350/220 to the B-cell CR2/CD21 receptor. After intracellular release from the capsid the linear DNA molecule forms a closed loop by fusion within the terminal regions. In latency, several copies of the circular episomal form remain in the nucleus, with host cell DNA polymerase-dependent replication limited to the cellular S phase, a feature that ensures partitioning of virus to all daughter cells. Under the influence of EBV latent transforming genes, infected B cells rapidly proliferate within lymphoid tissues until checked by a vigorous anti-viral immune response comprised of EBV-specific antibodies, EBV-specific cytotoxic T cells, and NK cells. Some EBV-infected B cells mature into plasma cells and switch from latency to lytic phase with end-stage virus replication. Following this initial phase, latent-infected B cells persist by severely limiting expression of EBV proteins, thus avoiding immune recognition. After recovery from primary infection, these quiescent long-lived EBV-infected memory B cells freely recirculate in blood and, in the healthy host, largely remain in a tightly latent state, with low-level lytic replication associated with plasmacytic differentiation. In the asymptomatic virus carrier state, continuous low-level lytic replication in the oral region leads to shedding of virus in saliva and persistence of an anti-viral immune response.

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  1. Department of Pathology and Laboratory Medicine, Director, Division of Hematopathology, Yale University School of Medicine, 310 Cedar Street, BML116B, New Haven, CT, 06520-8023, USA

    S. David Hudnall M.D., F.C.A.P.

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    S. David Hudnall

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Hudnall, S.D. (2014). Epstein–Barr Virus: Pathogenesis and Host Immune Response. In: Hudnall, S. (eds) Viruses and Human Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0870-7_2

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