Cytomegalovirus infection: friend or foe in rheumatoid arthritis?

Abstract

Human cytomegalovirus (HCMV) is a β-herpesvirus that causes inflammation and remains for life in a latent state in their host. HCMV has been at the center of many hypotheses regarding RA.We have recently shown that HCMV infection impairs bone erosion through the induction of the mRNA-binding protein QKI5. Latently infected RA patients display a slower progression of bone erosion in patients from a national cohort. Our observations question the possible association between HCMV and the pathophysiology of RA. In this review, we examine the possibility that HCMV may be an aggravating factor of inflammation in RA while protecting from bone erosion. We also assess its relationship with other pathogens such as bacteria causing periodontitis and responsible for ACPA production.This review thus considers whether HCMV can be regarded as a friend or a foe in the pathogenesis and the course of RA.

Keywords: Bone erosion; Cytomegalovirus; Inflammation; Osteoclast; QKI5; Rheumatoid arthritis.

Fig. 1

Overview of the mechanistic role of HCMV in the articular damage in RA. Infection of monocytes by HCMV induces QKI5 that inhibits the expression of CSF-1R and inhibits CIITA. Consequently, OC differentiation is inhibited. Infected monocytes differentiate into “M1-like” macrophages that produce pro-inflammatory cytokines and help fibroblasts produce metalloproteases. Production of viral IL-10 may contribute to perpetuate to decreased OC differentiation. Contribution to the inhibition of OC differentiation may be due to IFN-γ produced by “M1-like” macrophages