探討抗病毒藥物對人類微小病毒B19-VP1u蛋白功能之影響

The effect of anti-viral drugs on protein function of human parvovirus B19-VP1u

茆耿嘉(Geng-Jia Mao)

指導教授 ： 徐再靜

中山醫學大學/醫學院/生化微生物免疫研究所/碩士(2019年)

https://doi.org/10.6834/CSMU201900049

摘要

人類微小病毒 B19是一個單股核苷酸DNA的病毒，其基因編碼出三種主要蛋白，非結構蛋白NS1及結構蛋白VP1和VP2，其中VP1比VP2多了227個胺基酸，稱為人類微小病毒結構蛋白獨立區域 B19-VP1u。文獻指出B19-VP1u具有一段磷脂質分解酶A2(PLA2) motif，可促進老鼠巨噬細胞 Raw264.7 活化及 MMP-9與發炎性細胞激素IL-6 和TNF-α 的表現。人類微小病毒 B19感染到目前為止仍然沒有有效之抗病毒藥物來治療，因此我們利用臨床上常用的抗病毒藥物Ribavirin、Oseltamivir、Lamivudine、Acyclovir來探討對人類微小病毒 B19-VP1u重組蛋白功能的影響。由研究結果得知，Lamivudine、Deherp 會抑制B19-VP1u的 sPLA2活性。Ribavirin 、Oseltamivir會抑制B19-VP1u刺激後的Raw 264.7細胞存活率。Oseltamivir 會提升B19-VP1u的 sPLA2活性與抑制MMP-9與發炎性細胞激素IL-6的表現，減緩發炎反應的發生。Ribavirin 在合理的使用量時，能有效的抑制MMP-9與發炎性細胞激素TNF-α的表現，
減緩發炎反應。雖然Ribavirin 與Oseltamivir 抑制人類微小病毒B19
的機制尚不清楚，但此研究結果將可提供作為未來治療人類微小病毒
B19 之抗病毒藥物中的潛力藥物方案參考。

關鍵字

人類微小病毒B19

並列摘要

Human parvovirus B19 is a single-nucleotide DNA virus that encodes three major proteins, the non-structural protein NS1 and the structural proteins VP1 and VP2. VP1 has 227 amino acids more than VP2, called VP1 unique region (VP1u).The literature indicates that a phospholipid degrading enzyme A2 (PLA2) motif is present at the N-terminus of B19-VP1u, which promotes the activation of mouse macrophage Raw264.7 and the expression of MMP-9 and inflammatory cytokines IL-6 and TNF-α. Human parvovirus B19 infection has not yet been effectively treated with antiviral drugs, so we used the clinical antiviral drugs Ribavirin, Lamivudine, Oseltamivir, Acyclovir to explore the drug effects on the function of recombinant protein B19-VP1u. According to the results of the study, Lamivudine and Deherp inhibit the sPLA2 activity of B19-VP1u. Ribavirin and Oseltamivir inhibit the survival rate of Raw 264.7 cells after B19-VP1u stimulation. Oseltamivir enhances the sPLA2 activity of B19-VP1u and inhibits the expression of MMP-9 and the inflammatory cytokine IL-6, slowing down the inflammatory response. Ribavirin can effectively inhibit the expression of MMP-9 and the inflammatory cytokine TNF-α at a reasonable dose, and
slow down the inflammatory response. Although the mechanism by which Ribavirin and Oseltamivir inhibit human parvovirus B19 is unclear, the results of this study will provide potential antiviral drugs for future treatment of human parvovirus B19 infection.

並列關鍵字

human parvovirus B19

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