The Epstein-Barr virus (EBV) is a common pathogen and a member of the human herpesvirus family. It is estimated that over 90% of the global adult population is infected with this virus. For many, the initial infection occurs without symptoms, but in adolescents and young adults, it is the primary cause of infectious mononucleosis. The virus establishes a lifelong, persistent infection within the body’s B lymphocytes, a type of white blood cell. Its structure is composed of several distinct layers, each with a specific role in protecting the viral genetics, evading the immune system, and executing the infection of host cells.
The Genetic Core and Protective Capsid
At the center of the Epstein-Barr virus lies its genetic material, a large double-stranded DNA molecule. This genome contains approximately 172,000 base pairs and encodes for more than 85 genes. These genes are the blueprint for all viral proteins, dictating the virus’s ability to replicate, assemble new particles, and manipulate the host cell’s machinery.
This genetic code is housed within a protective protein shell called the nucleocapsid. The capsid is assembled from protein subunits into a symmetric icosahedral shape, resembling a 20-sided die. This architecture provides robust protection for the viral DNA and is an efficient way to enclose a large volume.
The viral genome contains genes for both the active (lytic) and dormant (latent) phases of its life cycle. During latency, the virus can remain hidden within host cells for a lifetime. It persists by expressing only a limited set of genes, such as Epstein-Barr nuclear antigen 1 (EBNA-1), which avoids triggering a strong immune response.
The Amorphous Tegument Layer
Situated between the nucleocapsid and the outer viral envelope is a layer known as the tegument. Unlike the ordered structure of the capsid, the tegument is amorphous and lacks a defined shape. This protein-filled space contains a mixture of viral proteins that are important for the earliest stages of infection.
The tegument functions as a pre-packaged toolkit that the virus carries with it into a new host cell. Upon entry, these tegument proteins are immediately released into the cell’s cytoplasm, where they can begin to orchestrate a takeover of the cellular environment. This payload includes enzymes and transcriptional activators that help to suppress the host’s innate immune defenses and prepare the cell for viral gene expression.
Among the many proteins found in the tegument are molecules designed to counteract cellular antiviral responses. For example, the large tegument protein BPLF1 has been shown to interfere with the cell’s Toll-like receptor signaling pathways, which are a first line of defense against viral intruders.
The Viral Envelope and Surface Proteins
The outermost boundary of the Epstein-Barr virus is the viral envelope, a lipid membrane acquired as it buds from a host cell. This envelope is studded with viral glycoproteins that protrude from the surface. These glycoproteins are used to identify and attach to specific host cells to initiate infection.
The most abundant of these surface proteins is glycoprotein 350/220 (gp350/220). This protein acts as the primary attachment molecule, binding to a receptor called CD21 on the surface of B lymphocytes. This interaction is the first step in the infection process for B cells, anchoring the virus to its target. The high affinity between gp350/220 and CD21 is a major reason why B cells are the principal target for EBV infection.
For the virus to fully enter the cell, another set of glycoproteins is required to mediate the fusion of the viral envelope with the host cell membrane. This function is carried out by a complex of proteins: glycoprotein H (gH), glycoprotein L (gL), and glycoprotein 42 (gp42). While gH and gL are part of the fusion machinery for many herpesviruses, the inclusion of gp42 is specific to EBV’s mechanism for entering B cells. The interaction of this gH/gL/gp42 complex with the major histocompatibility complex (MHC) class II triggers the changes that lead to membrane fusion.
How Structure Enables Cellular Invasion
The structure of EBV is a coordinated system designed for cellular invasion. The process begins when the envelope’s glycoproteins attach the virus to a B lymphocyte. This anchoring allows other surface proteins to trigger the fusion of the viral and cellular membranes. Once fused, the nucleocapsid and tegument proteins are released into the cell. The tegument proteins immediately begin suppressing the cell’s defenses while the nucleocapsid travels to the nucleus to release the viral DNA, initiating infection.