人類微小病毒B19殼體蛋白獨立區域對狼瘡小鼠心臟影響之研究

人類微小病毒B19 (Human parvovirus B19, B19)是微小病毒科中會感染人類的病毒，殼體蛋白的組成中包含了VP1及VP2，VP1的N端具有一段227個胺基酸的序列，這段序列命名為VP1-unique region (VP1u)。許多文獻報導在心臟疾病患者的血液或是心臟組織中有B19病毒的蹤影，並且發現感染B19病毒與心肌炎之間有著相關性，但詳細機轉並不清楚。另一方面，感染B19病毒也經常被發現與自體免疫疾病之間有著關聯性，如紅斑性狼瘡(SLE)疾病。先前許多文獻指出感染B19病毒可能會誘發自體免疫反應而導致SLE發病的情況或促使SLE的病情更加惡化。在近幾年的研究，B19-VP1u被發現在B19病毒成功感染標地細胞及引起細胞發炎反應，扮演非常重要的角色。然而，B19-VP1u是否會造成心肌炎，並沒有相關文獻探討。因此本實驗利用NZB/W F1小鼠做為一個lupus-prone的模式，利用注射方式給予三組NZB/W F1小鼠(1) PBS，(2)兔子IgG抗體，(3)兔子VP1u IgG抗體，結果發現注射B19-VP1u抗體至NZB/W F1 狼瘡小鼠會促進血清天冬氨酸轉氨酶(AST)的表現。此外，實驗結果發現B19-VP1u抗體會促進心臟基質金屬蛋白酶MMP9活性及MMP9蛋白的表現並且透過NFκB蛋白訊息傳遞路徑。此外分析心肌梗塞相關蛋白h-fatty acid binding protein(h-FABP)和creatine kinase-M/B (CKMB)及心室肥大相關蛋白atrial natriuretic peptide (ANP)及brain natriuretic peptide (BNP)，結果發現B19-VP1u抗體並不會促進心臟表現心肌梗塞或心室肥大的情形。由此推測施打Anti-B19 VP1u IgG可能會直接或間接對於NZB/W F1小鼠心臟組織造成傷害。因此B19-VP1u和Anti-B19 VP1u IgG不僅增加SLE疾病的活動性，並且會造成心臟損傷和心肌發炎的情形產生。

關鍵字

人類微小病毒B19

並列摘要

Human parvovirus B19 is one of the Parvoviridae family and known to be pathologic in humans. The capsid of parvovirus B19 consists of two structural proteins, VP1 and VP2, which are identical except for 227 amino acids at the amino-terminal end of the VP1 protein. So the additional 227 amino acids at VP1 amino-terminus were called VP1-unique region (VP1u). Recently, more and more literatures assumed that there is a link between B19 infection and myocarditis, but the detailed mechanisms are still unknown. In addition, parvovirus B19 infection has been associated with autoimmune diseases including SLE. Some studies have supposed that B19 may exacerbate or even induce SLE. In recent research, B19 VP1u was discovered that the region played an important role in successful infection and inflammation response. However, fewer literatures discussed whether B19 VP1u could cause myocarditis. In this study, we used NZB/W F1 mice as a lupus-prone model and inoculated these mice with (1) PBS, (2) Rabbit IgG and (3) Rabbit anit-B19 VP1u IgG respectively. We found that NZB/W F1 mice inoculated with B19-VP1u IgG had higher Aspartate Aminotransferase level in sera. Besides, we found that B19-VP1u IgG promoted protein expression and activity of matrix metalloproteinase 9 in heart via NFκB pathway. Moreover, B19 VP1u IgG didn’t cause myocardial infarction or hypertrophy. All together, we supposed that B19-VP1u IgG inoculation might directly or indirectly cause mice myocardial damage. In conclusion, anti-B19 VP1u IgG inoculation not only aggravates disease activity of SLE, but also causes cardiac damage and inflammation.

並列關鍵字

Human Parvovirus B19

參考文獻

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人類微小病毒B19殼體蛋白獨立區域對狼瘡小鼠心臟影響之研究

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