**3.2. Cytomegalovirus**

Human cytomegalovirus (HCMV) or cytomegalovirus (CMV) is a large double-stranded DNA prototypic pathogenic member of the beta-subgroup of the herpesvirus family. Certain features attributed to the cytomegalovirus, like lytic replication in several different tissues, its lifelong persistence through periods of latency and reactivation, an extraordinarily large proteome, considerable manipulation of adaptive and innate immune systems, and its worldwide prevalence in human populations, make it a prominent candidate for involvement and exacerbation of autoimmune abnormalities [40]. Cytomegalovirus is known to be a leading cause of mental retardation and congenital hearing loss, and CMV infection is known to induce several autoimmune disorders in mice that resemble abnormalities in SLE [41]. It has also been implicated in the development and/or progression of SLE in humans [42]. Additionally, CMV has been associated with many other autoimmune diseases such as inflammatory bowel disease [43], diabetes mellitus [44, 45], systemic sclerosis [46], antiphospholipid syndrome [47, 48], and rheumatoid arthritis. The relationship between CMV infection and accelerated atherosclerosis [49, 50] is unclear, as conflicting data have been reported, and thus requires further investigation. A clear relationship between HCMV seroprevalence and disease has not been established. A higher prevalence of HCMV IgG antibodies would be expected in patients suffering from specific types of autoimmune diseases if HCMV is a causative agent for the onset of autoimmunity. The UL83 encoded pp65 matrix protein has been linked to autoantibodies in SLE patients [40]. Studies have found either higher HCMV-specific IgG titers [51] or higher frequencies of HCMV infection in patients with SLE [51, 52]. Moreover, in SLE patients with higher HCMV-specific IgG titers, more frequent autoantibodies could be detected [53, 54]. However, a clear cause-and-effect relationship between CMV infection and the creation of autoantibodies has yet to be ascertained. In a study of patients with SLE and some other autoimmune diseases such as Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, biliary cirrhosis, polymyositis, or different types of vasculitis, a higher prevalence of CMV-associated IgM antibodies was detected [52]. The role of CMV in the pathogenesis of various autoimmune diseases requires further investigation.
