Epstein-Barr virus in systemic autoimmune diseases

Abstract

Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

Figure 1

Epstein-Barr virus structure and infection of cells. Epstein-Barr virus (EBV) is comprised of a dsDNA genome inside an icosahedral capsid which is surrounded by the tegument and enclosed by a host cell membrane-derived envelope. During infection with EBV, different envelope glycoproteins (gps) (shown in different colors) induce viral entry. During viral entry of B-cells, viral gp350 binds to type 2 complement receptor (CD21) on B-cells, and via a complex of gp42, gH, and gL, fusion of the cell membrane and the viral envelope is induced through (major histocompatibility complex) MHC II on the B-cell. During viral entry of epithelial cells, viral BMRF2 binds to β1-integrins on the epithelial cell, and fusion of the membranes is facilitated by a complex of gH and gL. gp110 improves the efficiency of EBV to infect B-cells and epithelial cells. EBV can also infect T-cells; however, the mechanism of viral entry is unknown (?). BCR: B-cell receptor, TCR: T-cell receptor.