The Epstein-Barr virus, or EBV, is a member of the herpesvirus family and one of the most widespread human viruses, infecting over 90% of the global adult population. The virus contains a double-stranded DNA genome and is transmitted between people primarily through oral saliva. While infection in early childhood often occurs without noticeable symptoms, acquiring the virus during adolescence or young adulthood can lead to infectious mononucleosis in a significant percentage of cases.
The Primary Cellular Target: B Lymphocytes
The Epstein-Barr virus exhibits a specific preference for certain cells within the human immune system, with B lymphocytes being its principal target. The virus gains entry into these cells through an interaction between the viral glycoprotein gp350 and a protein on the B cell surface known as complement receptor type 2 (CR2), or CD21.
Once inside the B cell, EBV establishes a persistent, lifelong infection by entering a dormant state. This allows the virus to integrate its genetic material with the cell’s own. A notable consequence of this process is the “immortalization” of infected B cells, as the virus expresses genes that stimulate them to grow and divide indefinitely. This process is central to the development of infectious mononucleosis and its symptoms.
This unchecked proliferation of infected B cells spreads the virus throughout the body’s lymphatic system, including the liver, spleen, and peripheral lymph nodes. The body’s immune response to this widespread infection of B cells is what causes the familiar signs of mono, such as fever, fatigue, and a sore throat. The virus co-opts the B cell’s machinery for its own long-term survival and propagation.
Infection of Epithelial Cells
While B cells are the site of long-term infection, epithelial cells play a different role in the EBV life cycle. These cells, which form the lining of surfaces in the body, are significant targets in the oropharynx—the area at the back of the mouth and throat. Epithelial cells are often the site of the initial infection when the virus is first transmitted.
The mechanism for entering epithelial cells can differ from that of B cells. While some may express the same CD21 receptor, the virus can also use other combinations of proteins to gain entry. This flexibility to infect both cell types is a feature of its successful persistence in humans.
In contrast to the dormant state in B lymphocytes, the virus’s activity in epithelial cells is geared towards active replication, known as the lytic cycle. This is where the virus hijacks the cell’s machinery to produce a large number of new virus particles. These virions are then shed into saliva, which facilitates transmission to new hosts.
The Two Phases of Infection: Lytic and Latent Cycles
The persistence of Epstein-Barr virus is governed by two phases of its life cycle: latency and the lytic cycle. Latency is the default state for EBV, particularly within B lymphocytes. In this phase, the viral genome exists as a circular piece of DNA, known as an episome, inside the host cell’s nucleus with most of its genes silenced, hiding it from the immune system.
While dormant, the virus expresses a few proteins that encourage the host cell to survive and divide. This replicates the viral genome along with the cell’s own DNA. This strategy maintains a stable reservoir of the virus for the lifetime of the individual.
The lytic cycle is the active, replicative phase of the infection, which can be triggered by various stimuli. During this cycle, the full range of viral genes is expressed, turning the host cell into a factory for new virus particles. This process leads to the death of the host cell, releasing thousands of new virions to infect other cells or be transmitted to a new host.
Secondary and Rare Cellular Targets
Although B lymphocytes and epithelial cells are the main cell types infected by EBV, the virus is occasionally found in other immune cells, including T cells and Natural Killer (NK) cells. Infection of these cell types is less frequent and not part of the typical infection cycle.
These atypical infections are associated with more severe or unusual forms of EBV-related diseases. For instance, certain types of lymphomas derived from T cells or NK cells have been found to contain the Epstein-Barr virus. The presence of the virus in these cancers suggests it plays a role in their development.
The virus has also been detected in other cell types, such as histiocytic-dendritic cells. The study of these secondary targets is important for understanding the full spectrum of diseases linked to EBV, especially in individuals with compromised immune systems.