Epstein-Barr Virus Primarily Affects B Lymphocytes
EBV primarily infects and transforms B lymphocytes, though it can also infect T cells and NK cells under certain pathological conditions, particularly in chronic active EBV infection and specific lymphoproliferative disorders. 1
Primary Tropism: B Lymphocytes
- EBV is fundamentally a B-lymphotropic virus that establishes lifelong latent infection in memory B cells after primary infection 2, 3
- The virus uses CD21 (complement receptor 2) on B cells as its primary entry receptor, making B lymphocytes the natural target 1
- EBV-driven immortalization and transformation of B cells is the hallmark mechanism of viral pathogenesis, mediated by viral proteins that hijack cellular signaling pathways controlling B cell growth and survival 2
- In immunocompetent hosts, EBV colonizes memory B lymphocytes and remains there asymptomatically for life 2
B Cell-Mediated Disease Manifestations
- Post-transplant lymphoproliferative disorders (PTLD) arise predominantly from EBV-infected B lymphocytes in immunosuppressed patients 1, 2
- The oncogenic potential of EBV relates specifically to its ability to transform and immortalize B lymphocytes, leading to uncontrolled proliferation 1
- EBV-associated B-cell lymphomas express different latency patterns (latency I, II, or III) depending on the specific disease entity 1
- In immunocompromised individuals, EBV-lymphoproliferative disease expresses all viral nuclear antigens (EBNAs), latent membrane proteins (LMPs), and EBV-encoded RNAs (EBERs), representing latency III pattern 1
T Cell and NK Cell Involvement: The Exception
While B cells are the primary target, EBV can infect T cells and NK cells in specific pathological contexts:
- In chronic active EBV infection (CAEBV), the virus distinctly targets cells other than B lymphocytes, including T cells and NK cells 1
- Modern detection techniques (double-staining, in situ hybridization, magnetic bead procedures) have demonstrated EBV infection in T cells and NK cells in CAEBV patients 1
- Patients with CAEBV often develop T-cell or NK-cell lymphoproliferative disorders and malignant lymphomas during disease progression 1
- Recent studies showed that cells infected with EBV in CAEBV patients were not positive for CD8, suggesting deficient cytotoxicity as a causative mechanism 1
- Trans-synaptic acquisition of the EBV receptor CD21 from infected B cells may explain the unusual infection of NK cells 1
Immune Response Context
- EBV-specific cytotoxic T lymphocytes (CTLs) are the most important immune mechanism for controlling EBV-infected B cell proliferation 1, 4
- CD8+ CTLs target viral proteins EBNA-2, EBNA-3 family, and LMP-1 expressed on infected B cells 1, 4
- T cells function as regulators and effectors against EBV infection rather than primary viral targets 5, 6
- Suppressor T cells become activated during acute infectious mononucleosis to inhibit EBV-induced B cell activation 6
Clinical Pitfall to Avoid
Do not confuse T cell involvement in immune surveillance with primary viral tropism. While T cells play a critical role in controlling EBV infection and can become infected in pathological states like CAEBV, the virus fundamentally targets and transforms B lymphocytes in the vast majority of clinical scenarios 1, 2, 3. The presence of EBV in T cells or NK cells should prompt consideration of CAEBV or specific T-cell/NK-cell lymphoproliferative disorders rather than typical EBV infection 1.