人類微小病毒B19-VP1u蛋白對Balb/c小鼠肝臟影響之探討

人類微小病毒B19是微小病毒科中可以感染人類並且致病的病毒。過去研究證據顯示肝臟疾病患者之血液或是肝臟組織中有B19病毒蹤影，許多文獻也指出感染B19病毒與肝臟發炎損傷有關。近幾年研究發現B19-VP1u的磷脂酶A2區域(phospholipase A2 motif)與B19病毒感染細胞及引起發炎反應有密切關係，但是詳細機轉仍不清楚。本篇研究利用轉染技術將VP1u蛋白表現在COS-7 細胞，經由皮下注射方式打入Balb/c小鼠並利用IVIS非侵入式活體影像系統進行觀察，探討B19-VP1u對Balb/c小鼠之影響和發炎反應分子機制。結果發現B19-VP1u會促進Balb/c小鼠肝臟基質金屬蛋白酶(MMP9)活性及蛋白表現並活化磷酸化蛋白p38和ERK及IKK-α、IκB與NF-κB訊號傳遞分子。此外，發炎相關蛋白C-Reactive Protein (CRP)、IL-1β及IL-6蛋白表現也明顯增加並透過磷酸化蛋白STAT-1訊號傳遞引起肝臟發炎損傷。由實驗結果結果顯示B19-VP1u可引發肝臟損傷的免疫致病機轉。

關鍵字

人類微小病毒B19 ；肝臟； VP1u ；活體影像系統

並列摘要

Human Parvovirus B19 is a significant human pathogen in Parvoviridae. It has been re-ported that B19 can be detected in blood or liver specimens in patient with liver diseases. Indeed, various studies have postulated a connection between B19 infection and liver injury. Recently, studies suggested that the PLA2 motif of B19-VP1u play an important role in closely associated with B19-infected and inflammatory. However, the precise mechanism is still obscure. In the present study, we aimed to investigate the influence of B19-VP1u in Balb/c mice by injected subcutaneously with COS-7 cells expressing VP1u and observed using a non-invasive IVIS bio-luminescent imaging system. Our experimental results revealed that enhanced MMP-9 activity and increased phosphorylation of p38, ERK, IKK-α, IκB and NF-κB(p65) proteins in liver from Balb/c mice receiving B19-VP1u. Additionally, significantly increased inflammatory associated proteins, including CRP, IL-1β and IL-6 were observed in liver from Balb/c mice receiving B19-VP1u. Notably, phosphorylated STAT1 proteins were involved in the induction of inflammatory cytokines in liver from Balb/c mice receiving B19-VP1u. Our findings revealed the effects of B19-VP1u on liver injury and provide a clue in understanding the role of immuno-pathogenesis of B19-VP1u.

並列關鍵字

Human Parvovirus B19 ； Liver ； VP1u ； IVIS

參考文獻

1. Cossart YE, Field AM, Cant B, Widdows D: Parvovirus-like particles in human sera. Lancet 1975, 1(7898):72-73.

2. Siegl G, Bates RC, Berns KI, Carter BJ, Kelly DC, Kurstak E, Tattersall P: Characteristics and taxonomy of Parvoviridae. Intervirology 1985, 23(2):61-73.

3. Pattison JR, Jones SE, Hodgson J, Davis LR, White JM, Stroud CE, Murtaza L: Parvovirus infections and hypoplastic crisis in sickle-cell anaemia. Lancet 1981, 1(8221):664-665.

4. Serjeant GR, Topley JM, Mason K, Serjeant BE, Pattison JR, Jones SE, Mohamed R: Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet 1981, 2(8247):595-597.

5. Zhi N, Mills IP, Lu J, Wong S, Filippone C, Brown KE: Molecular and functional analyses of a human parvovirus B19 infectious clone demonstrates essential roles for NS1, VP1, and the 11-kilodalton protein in virus replication and infectivity. Journal of virology 2006, 80(12):5941-5950.

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人類微小病毒B19-VP1u蛋白對Balb/c小鼠肝臟影響之探討

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