Virology, Nebraska Center for



Luwen Zhang

Date of this Version



Published in Journal of Medical Virology 95:1 (2022), e28363



Copyright © 2022 Wiley Periodicals LLC. Used by permission.


Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play a promotional role in majority of the autoimmune diseases by repeated replenishment of EBV type III latency cells and inflammatory cytokine productions in persistent stage. The type III latency cells have enhanced capacity as antigen‐presenting cells that would facilitate the development of both B and T cell‐mediated autoimmunity. The repeated cytokine productions are achieved by the repeated infection of naive B‐lymphocytes and proliferation of type III latency cells that produce inflammatory cytokines. Presentation of viral or self‐antigens by EBV type III latency B lymphocytes may promote autoreactive B cell and T cell proliferation, which can be amplified by type III latency cells‐mediated cytokines productions. Different autoimmune diseases may require different kinds of pathogenic immune cells and/or specific cytokines. Frequency of the replenishment of EBV type III latency cells may determine the specific effect of the promoter functions. A specific initiator plus EBV‐mediated common promoter function may lead to development of a