Mouse model for acute Epstein-Barr virus infection.

Area of Science:

• Virology
• Immunology
• Oncology

Background:

• Epstein-Barr virus (EBV) infects B cells, causing continuous proliferation via latent membrane proteins (LMP1, LMP2A).
• EBV-induced B-cell proliferation is normally controlled by T-cell responses, but immune evasion can lead to lymphomas.
• Defects in immune surveillance of EBV-infected cells cause severe lymphoproliferative disorders.

Purpose of the Study:

• To model EBV infection in mice using timed expression of LMP1 and LMP2A in B cells.
• To investigate the role of T-cell responses in controlling EBV-driven B-cell proliferation and lymphomagenesis.
• To explore the impact of LMP1 and LMP2A expression in different B-cell subsets (naive vs. germinal center).

Main Methods:

• Induction of LMP1 and LMP2A expression in subsets of naive and germinal center B cells in mice.
• Monitoring B-cell expansion and T-cell responses following viral protein expression.
• Assessing the impact of T-cell activity and perforin deficiency on disease progression.

Main Results:

• Inducing LMP1/LMP2A in a small fraction of naive B cells caused transient expansion followed by T-cell-mediated clearance.
• Interfering with T-cell activity or perforin function prevented clearance and led to B-cell expansion.
• LMP expression in germinal center B cells impaired the GC reaction and caused fatal expansion without T-cell surveillance.

Conclusions:

• Timed expression of LMP1 and LMP2A in mouse B cells effectively models key aspects of human EBV infection.
• T-cell surveillance is critical for controlling EBV-driven lymphoproliferation.
• This model provides a platform for studying EBV pathogenesis and developing new therapeutic strategies.