2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38592The association of human parvovirus B19 infection and autoimmune diseases with autoantibodies has been strongly suggested in these years, but the molecular basis and pathogenesis of B19-induced autoimmune phenomena is unclear. B19 is a small single-stranded DNA virus containing 5596 nucleotides, which has three large open reading frames. The B19 encodes two structural proteins, the major capsid (VP2) and minor capsid (VP1) proteins, and a nonstructural protein (NS1). VP1 has an identical amino-acid sequence to VP2 protein, and exception for an additional 227 amino acids at its amino terminus (VP1 unique region, VP1u). Moreover, phospholipase A2 (PLA2)-like activity has been linked to the VP1u of B19. Recent studies indicated that VP1u mutant in the phospholipase domain loses its activity, proportionally, and viral infectivity Previously, we have found that B19 infection may be linked to the induction of autoimmune responses and autoantibdies [Lupus 2000; 9: 551-554.; Rheumatology (Oxford). 2001;40:152-7]. Recently, we found that the association of VP1 unique region protein in acute parvovirus B19 infection and antiphospholipid antibody (aPL) production [Clinica Chimica Acta 2007; 378: 59-65.]. These results suggest B19-VP1u may have contributed to the production of aPL. Moreover, adsorption experiment revealed the partially reduced reactivity of anti-B19VP1u antibody to cardiolipin (CL) and β2-glycoprotein I (β2GPI) suggesting similar epitopes or conformation may exist between B19-VP1u, CL and β2GPI. Recently, we found that sera from rabbits immunized with recombinant B19-VP1u protein displayed raised detectable immunoglobulins against B19-VP1u, CL, β2GPI and PhL. Additionally, the mice immunized with anti-B19-VP1u IgG developed thrombocytopenia, prolongation of aPTT, and autoantibody against β2GPI and PhL. These experimental results suggested the association between B19-VP1u and production of APhL and APS-like autoimmunity [Clinica Chimica Acta 2007; 382: 31-36]. Thus, these observations encouraged us to study more about the link between B19-VP1u on B19 infection and autoimmunity. To elucidate the role of VP1u in autoimmunity, the goals of this research and future prospective are: 1. Analyze the molecular effect of Balb/c mice or immune-disease mouse model with anti-B19-VP1u antibody. 2. Analyze the molecular effect of VP1u and anti-VP1u antibodies on macrophages, trophoblast cells, venous endothelial cells and anti-phospholid syndrome. 3. Genomic and proteomic study on the molecular mechanism of human parvovirus B19-VP1 unique region and anti-B19-VP1u antibody on induction of autoimmunity. These data will help us to know more of the role and molecular mechanism of VP1u on B19 infection and autoimmunity, and maybe useful as a basis for the development and protection against parvovirus B19 infection and autoimmune diseases.感染人類微小病毒B19 (B19)會表現許多自體免疫症狀及自體抗體，但詳細機轉不明。 B19 屬於小病毒(Parvoviridae)且無套膜之單股DNA 病毒，基因約為5600 bases。主 要由兩個殼體蛋白(結構蛋白)〔VP1 (781 amino acids [aa]) 和VP2 (554 aa)〕和 非結構蛋白NS1 所組成。這兩個殼體蛋白除了VP1 比VP2 在N 端多了227 amino acids 外，它們有著相同的open reading frame 序列，而這多出的序列已被命名為結構蛋白 獨立區域[VP1 unique region (VP1u)]。而近年的研究發現VP1u 和B19 中和抗體、 病毒感染有關且其序列具有類似phospholipase A2 (PLA2) 之motif。 過去我們實驗室發現B19 感染會造成自體抗體的產生，包括抗嗜中性白血球細胞質抗 體(ANCA)和抗牛心脂抗體(aCL)〔Lupus 2000; 9: 551-554]。另外也發現在全身性紅斑性 狼瘡病人血清中有B19 DNA 的存在，而這些全身性紅斑性狼瘡患者也被發現如果檢測 結果是沒有B19 抗體的病人比有B19 抗體的病人較常發現具有B19 DNA (p<0.05)〕〔 Rheumatology (Oxford). 2001; 40: 152-7.]。最近更發現急性感染B19 的病人，血清中的 抗牛心脂抗體和抗β2GPI 抗體(抗磷脂質抗體)可能和結構蛋白獨立區域VP1u 有關係 [Clinica Chimica Acta 2007; 378: 59-65.]。為了釐清是否VP1u 會被抗磷脂質抗體所辨 識，我們更進一步進行動物實驗研究，結果發現將抗B19-VP1u 抗體打入Balb/c 老鼠 體內可誘發抗磷脂質抗體及類似抗磷脂質症候群症狀的產生[Clinica Chimica Acta 2007; 382: 31-36.]。這是一項新且重要的發現。這些研究結果顯示VP1u 在B19 感染和 自體免疫之間確實扮演居中誘導的角色。然而這部分的機制仍不清楚，所以我們將探 討VP1u 和抗VP1u 抗體誘發自體免疫之分子機轉。我們將探討以下問題： 1. 免疫注射抗VP1u 抗體至正常鼠及自體免疫疾病模式小鼠並分析宿主體內具有抗 VP1u 抗體存在情況下其血液、組織和細胞之影響及參與訊息傳遞分子機轉 2. 探討VP1u 抗原和抗VP1u 抗體及抗磷脂質抗體對於巨噬細胞和血管內皮細胞及胎 盤滋養層母細胞之影響與抗磷脂質症候群之關係及其分子機轉 3. 以基因體及蛋白體技術探討VP1u 抗原及抗體對於宿主感染B19 和誘導自體免疫反 應產生之機制 希望藉由以上這些研究，能讓我們可以更進一步了解到VP1u 和VP1u 抗體在B19 感染 誘發自體免疫之免疫分子作用機制，並提供作為未來治療或防治B19 感染和自體免疫 疾病產生的參考。Project