Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown aetiology. The major hallmark of this disease is the presence of antibodies against nuclear components, including double-stranded (ds)DNA and histones. The disease affects different organs, particularly the skin, kidneys and the nervous system. Although the exact molecular mechanisms underlying the pathophysiological processes in SLE remain unknown, several inherent and environmental factors seem to be involved in the ethiopathogenesis of this disorder. Viruses may be one of the factors that induce the production of autoreactive antibodies although the involved mechanisms are still incompletely understood. One proposed mechanism for virus-induced production of autoantibodies is molecular mimicry. Another mechanism derives from studies with the human polyomavirus BK. In these studies, in vivo binding of the polyomaviruses large T-antigen to chromatin of infected cells may render chromatin immunogenic. The large T-antigen-chromatin complex may thus function as a hapten-carrier model with subsequent production of anti-chromatin antibodies, including anti-dsDNA and anti-histones antibodies. This review focuses on the recent findings suggesting that this model may be applicable for other human viruses associated with SLE.