tailieunhanh - Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen

Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure. Methods: To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear. | Tzang et al. Journal of Biomedical Science 2010 17 40 http content 17 1 40 a NSC The cost of publication In Journal of Blomodlcal Science Is bome by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen Bor-ShowTzang1 2 3 Der-Yuan Chen4 5 6 Chun-Chou Tsai7 Szu-Yi Chiang8 Tsung-Ming Lin7 and Tsai-Ching Hsu 3 7 Abstract Background Human parvovirus B19 B19 is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein NS1 induces mitochondrial-dependent apoptosis in COS-7 cells the precise mechanism of B19-NS1 in developing autoimmunity is still obscure. Methods To further examine the effect of B19-NS1 in presence of autoantigens COS-7 cells were transfected with pEGFP pEGFP-B19-NS1 and pEGFP-NS1 K334E a mutant form of B19-NS1 and detected the expressions of autoantigens by various autoantibodies against Sm U1 small nuclear ribonucleoprotein U1-snRNP SSA Ro SSB La Scl-70 Jo-1 Ku and centromere protein CENP A B by using Immunoblotting. Results Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP Meanwhile the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product which were recognized by anti-U1-snRNP autoantibody. In contrast significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1. Conclusions These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP. Background Human parvovirus B19 B19 has been associated with the development of .