Increasing hepatic diseases are reported in SLE patients and recognized as important consequences of SLE, which also links to the pathogenesis of SLE. Indeed, a previous study indicated that 11 SLE patients showed liver abnormality including fatty change, portal tract fibrosis, cellular infiltration, or even cirrhosis. Another study of patients with SLE indicated that 124 of 206 patients tested had at least one abnormal result, and 43 met strict criteria for the existence of liver disease. Similar results were also reported in lupus-prone animal models. These findings strongly indicated the significant association of liver abnormality including fibrosis in SLE. Human parvovirus B19 is known as an erythrovirus of human pathogen that consists a nonstructural protein and two capsid proteins, VP1 and VP2. Recently, evidences have indicated that human parvovirus B19 may exacerbate or even induce SLE and postulated a connection between these B19 viral proteins and the pathogenesis of SLE. However, the effects of B19 viral proteins on liver fibrosis in SLE are still obscure. In the current study, we treated NZB/W F1 mice by injecting subcutaneously with recombinant B19 NS1, VP1u and VP2 proteins to investigate the effects of these B19 viral proteins on liver fibrosis in SLE. Human parvovirus B19 is recognized as a trigger to exacerbate SLE. Although B19 has been postulated to the pathogenesis of SLE in a variety of organs including liver, little is known about the effects of B19 viral proteins on hepatic fibrosis in SLE. In the present study, we firstly reported the aggravated effects of human parvovirus B19 NS1 protein on hepatic fibrosis in NZB/W F1 mice. Significant increases of TGFb/Smad fibrotic signaling were detected in livers from NZB/W F1 mice receiving B19 NS1 protein via increasing the expressions of TGF-b, Smad2/3, p-Smad2/3, Smad4 and Sp1. Accordingly, the consequent fibrosis-related proteins, PAI-1 and a-SMA, were significantly induced in livers from NZB/W F1 mice receiving B19 NS1 protein. Meanwhile, markedly increased collagen deposition was also observed in livers from NZB/W F1 mice receiving B19NS1 protein. Increasing evidences have indicated the pivotal characters of various cytokines such as interleukin-6, TGF-b in the progression of hepatic fibrosis. Indeed, a positive correlation between IL-6 expression in hepatocytes and the severity of hepatic fibrosis in patients with non-alcoholic fatty liver disease was observed. Another study also reported that polymorphisms induce high angiotensinogen and TGF-b1, the most abundant isoform of TGF-b, are associated with advanced hepatic fibrosis in patients with NAFLD. Although a recent study of 12 clinical cases represented the associations of B19 infection with fibrotic diseases including idiopathic pulmonary fibrosis, scleroderma-associated pulmonary fibrosis, lymphocytic interstitial pneumonitis, and septal capillaritis, the effects of B19 on hepatic fibrosis in SLE are still obscure.