Cytomegalovirus-induced immunopathology and its clinical consequences

Abstract

Human cytomegalovirus (CMV) is a ubiquitous DNA virus that causes severe disease in patients with immature or impaired immune systems. During active infection, CMV modulates host immunity, and CMV-infected patients often develop signs of immune dysfunction, such as immunosuppression and autoimmune phenomena. Furthermore, active viral infection has been observed in several autoimmune diseases, and case reports have linked primary CMV infection and the onset of autoimmune disorders. In addition, CMV infection promotes allograft rejection and graft-versus-host disease in solid organ and bone marrow transplant recipients, respectively, further implicating CMV in the genesis and maintenance of immunopathological phenomena. The mechanisms by which CMV could induce inhibition of host defense, inflammation, and autoimmunity are discussed, as is the treatment of virus-induced immunopathology with antivirals.

Figure 1

Mechanisms by which CMV can induce host immunopathology. A; CMV-induced autoantibody production. B; Enhanced inflammation caused by the virus. C; CMV-induced vascular damage and vessel thickening. D; CMV-induced immunosuppression. TLR7/9; toll-like receptor 7/9, PDC; plasmacytoid dendritic cell, SMC; smooth muscle cell, 5-LO; 5-lypooxygenase, cox-2, cyclooxygenase-2, PGE2; prostaglandin E2, LTB4; leukotriene B4, MIF; macrophage migration inhibitory factor, MIP-1α; macrophage inflammatory protein 1-α, MIP-1β; macrophage inflammatory protein 1-β, VCAM-1; vascular cell adhesion molecule-1, PDGF; platelet-derived-growth factor, vIL-10; virally encoded IL-10. Modified from: Varani et al. "Cytomegalovirus-induced autoimmunity" in "Autoimmune Disorders: Symptoms, Diagnosis and Treatment". Editor: M.E. Petrov. ISBN: 978-1-61761-552-8; ^© 2010 Nova Science Publishers, Inc.

Figure 2

CMV-induced immunopathology in various groups of patients--previously healthy subjects, immunodepressed transplant recipients, and patients with autoimmune disorders. Modified from: Varani et al. "Cytomegalovirus-induced autoimmunity" in "Autoimmune Disorders: Symptoms, Diagnosis and Treatment". Editor: M.E. Petrov. ISBN: 978-1-61761-552-8; ^© 2010 Nova Science Publishers, Inc.