臺灣博碩士論文加值系統

摘要
傳染性胰臟壞死病毒（infectious pancreatic necrosis virus, IPNV-T42G），屬於兩段雙股核醣核酸病毒科，目前是養殖漁類重要的病源之一。雖然IPNV在1960年代的早期就已經被分離出來，但是對於病毒如何誘導細胞中分子的改變以有利於病毒複製之調節機制的瞭解卻很少，故本論文主要在於探討病毒對細胞週期的調節以及細胞訊息傳遞之影響，在病毒感染複製過程中所扮演的角色。
許多病毒感染細胞後會影響細胞的分裂週期，以利於病毒的複製，本實驗以流式細胞分析技術分析CHSE-214被IPNV感染後細胞週期的變化，當病毒感染細胞週期停止在G0/G1期的細胞時，在病毒感染後的3小時內，病毒會將細胞週期停留在G0/G1-S的過渡期（78.3%的細胞在G0/G1期，12.4%在S期，9.17%在G2/M期）。這個結果說明IPNV會阻止CHSE-214細胞細胞週期的正常運行，在感染後的3小時內，IPNV會調節細胞週期以抑制細胞週期之進行。
有許多DNA 或RNA病毒在感染細胞後會誘導細胞MAPK家族訊息傳遞路徑的活化，由西方墨點法分析CHSE-214被純化過的IPNV或經UV照射過的純化IPNV吸附後細胞訊息傳遞的變化，細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會造ERK1/2以及轉錄因子CREB的磷酸酯化，同時也會抑制JNK以及p38的活性，然而病毒的吸附卻不會影響IκBα的活性，IκBα是轉錄因子NF-κB的抑制子。這些發現說明了細胞在吸附不具有感染能力的純化IPNV後就會誘導細胞訊息的傳遞，此過程並不需要病毒的基因表現，而病毒的基因表現會造成第二次的磷酸酯化作用。

Abstract
Infectious pancreatic necrosis virus (IPNV) belongs to the Birnaviridae family. It is currently one of the most serious infectious diseases in fish farming. Though IPNV was originally isolated as long as early 1960s, little is known about the mechanism related to the viral induced intracellular molecular changes that support viral replication.
In this thesis we try to assess the cell cycle progression of the infected cells and to assess the potential role of cellular signal transduction in
IPNV replication.
Infection of cells by many viruses affects the cell division cycle of their host cells to favor viral replication. The cell cycle progression was performed by flow cytometry analysis, when CHSE-214 cells synchronized by growth inhibition were infected with IPNV. IPNV infected cells were arrested in the a G0/G1 phase at 3h after infection (78.3% of the cells in the G0/G1 phase, 12.4% in the S phase, and 9.17% in the G2/M phase). The result indicats that IPNV prevent normal cell cycle progression of CHSE-214 and the event is triggered early after virus infection by specific interaction with cellular components that regulate cell cycle progression.
A variety of DNA and RNA viruses induce signaling through MAP kinase family cascades in infected cells. The Western blot analysis of the phosphorylated protein was performed in CHSE-214 cells absorbed purified IPNV which was UV irradiated or untreated when cells were starved by the medium with no serum. ERK and CREB were phosphorylated in CHSE-214 after IPNV or UV-irradiated IPNV absorption, while JNK and p38 were dephosphorylated. However, IPNV absorption did not affect the activity of IκBα, an inhibitor of transcription factor NF-κB. The results indicate that IPNV initiates a signaling pathway without viral gene products and viral gene products may lead to the second time kinase activation.

目錄
摘要 I-II
Abstract III-IV
目錄 V-VII
圖表目錄 VIII-IX
壹、緒言
一、傳染性胰臟壞死病毒
1. IPNV的分類 1
2. IPNV的分怖 2
3. IPNV的感染症狀與寄主範圍 2-3
4. IPNV的生長、生物物理與生化特性 3-4
5. IPNV的遺傳物質與蛋白質功能 4-7
6. IPNV與其它緊迫因子對水生生物的影響 7-8
7. IPNV的診斷方法 8
二、細胞週期的控制 9-12
三、訊息傳遞的調控 12-15
四、訊息傳遞在細胞週期所扮演的角色 16-17
貳、材料與方法
一、材料
1. 細胞株 18
2. 病毒 18
3. 藥品 18-20
二、方法
1. 細胞之培養 20
2. 病毒之增殖、virion的純化與力價測定 20-23
3. 流式細胞技術之分析 23-24
4. 西方墨點法之分析 24-26
貳、結果
一、IPNV感染CHSE-214可以抑制細胞週期的進行 27-28
二、純化之病毒會失去感染能力 28-30
三、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會磷酸酯化ERK 30-32
四、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會抑制p38 32
五、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會抑制JNK 33
六、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都不會改變IκBα的活性 34
七、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會磷酸酯化CREB 35
參、討論
一、IPNV感染CHSE-214可以抑制細胞週期的進行 36
二、其他病毒調節細胞週期的機制與未來研究方向 36-38
三、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會磷酸酯化ERK 39-40
四、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會抑制p38 40
五、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會抑制JNK 41
六、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都不會改變IκBα的活性 42
七、細胞在吸附純化的IPNV或經UV照射的純化IPNV後都會磷酸酯化CREB 43
八、結語 44
伍、參考文獻 45-60
陸、圖表
圖表目錄
Table 1 The effects of HBSS, purified IPNV, unpurified IPNV or M10 on CHSE-214 cell cycle progression.
Table 2 Densitometry analysis of the Western blot.
Fig. 1 IPNV infection leads the cell cycle to arrest at G0/G1 phase.
Fig. 2 The effects of HBSS, purified IPNV, unpurified IPNV and M10 on cell cycle progression.
Fig. 3 The effects of IPNV on phosophorylated ERK levels in CHSE-214.
Fig. 4 The effects of IPNV deposited under the UV light for 15min on phosophorylated ERK levels in CHSE-214.
Fig. 5 The effects of IPNV on phosophorylated p38 levels in CHSE-214.
Fig. 6 The effects of IPNV deposited under the UV light for 15min on phosophorylated p38 levels in CHSE-214.
Fig. 7 The effects of IPNV on phosophorylated JNK levels in CHSE-214.
Fig. 8 The effects of IPNV deposited under the UV light for 15min on phosophorylated JNK levels in CHSE-214.
Fig. 9 The effects of IPNV on phosophorylated IκBα levels in
CHSE-214.
Fig. 10 The effects of IPNV deposited under the UV light for 15min on phosophorylated IκBα levels in CHSE-214.
Fig. 11 The effects of IPNV on phosophorylated CREB levels in CHSE-214.
Fig. 12 The effects of IPNV deposited under the UV light for 15min on phosophorylated CREB levels in CHSE-214.
附圖1 Organization of the genome of Birnaviridae and coding assignments.
附圖2 Signal transduction pathway of ERK.
附圖3 Signal transduction pathway of p38.
附圖4 Signal transduction pathway of JNK.
附圖5 Signal transduction pathway of IκB.
附圖6 Signal transduction pathway of CREB.

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