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

Bor-Show Tzang,Szu-Yi Chiang,Der-Yuan Chen,Tsai-Ching Hsu,Tsung-Ming Lin,Chun-Chou Tsai

doi:10.1186/1423-0127-17-40

Abstract

BackgroundHuman 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.MethodsTo 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 ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting.ResultsSignificantly 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.ConclusionsThese findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.

Highlights

Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders
The COS-7 cells transfected with pEGFP, pEGFPNS1, or pEGFP-NS1K334E were observed under phase contrast and fluorescence microscope (Fig 1A)
Cleavage apoptotic70-kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-NS1 Since B19-NS1 has been known to induce apoptosis and linked to the pathogenesis of autoimmune disorders, we further examined the presence of various autoantigens, including Sm, U1-snRNP, SSA, SSB, Scl-70, Jo-1, Ku, centromere protein (CENP)-A/B

Summary

Introduction

Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. 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. Human parvovirus B19 (B19) has been associated with the development of various autoimmune disorders [1,2,3,4,5,6,7]. Evidences have indicated that many clinical features in patients with acute or chronic B19 infection are extremely similar to those with autoimmune diseases, including the elevated levels of autoantibodies [5,6,8,9,10]. B19-NS1 protein has been reported to act as a transactivator of the B19 viral p6 and various cellular promoters

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Results

Conclusion