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研究生:張翠芸
研究生(外文):Tsui-yun Chang
論文名稱:D型肝炎小型抗原表現在秀麗隱桿線蟲咽喉造成生長遲滯現象之研究
論文名稱(外文):Study on Caenorhabditis elegans Growth Retardation Induced by Small Hepatitis Delta Antigen Expression in Pharynx
指導教授:羅時成
指導教授(外文):Szecheng J. Lo
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:72
中文關鍵詞:秀麗隱桿線蟲D型肝炎病毒
外文關鍵詞:Caenorhabditis elegansSmall Hepatitis Delta Antigenhepaptitis delta virus
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D 型肝炎病毒 ( hepaptitis delta virus, HDV )為一缺陷型病毒,必
需與B 型肝炎病毒 ( hepaptitis B virus, HBV )同時感染 ( coinfection )
或重複感染 ( superinfection ) 方可完成生活史。合併感染HBV 及
HDV 的病患,形成慢性肝炎、猛爆性肝炎、肝硬化、甚至肝癌的比
例均較單獨感染HBV 為高,但其分子層次的機制不明。因HDV 可
產生兩種大小不同的蛋白:large delta antigen ( LDAg )和small delta
antigen ( SDAg ),懷疑此兩抗原有可能與宿主細胞的分子作用而產生
症狀。本實驗室利用秀麗隱桿線蟲( Caenorhabditis elegans, C. elegans )
生活史短、容易操作,並有清楚的遺傳學建立分子途徑的特色建立研
究病毒之平台。在先前的實驗中發現:在轉殖線蟲咽喉部 ( pharynx )
表現HDV 的SDAg 會使線蟲有生長遲緩,及生育力降低的現象。本
實驗為了知道此抗原何段具有作用,將不同長度之SDAg 分別命名為
SD441、SD327、SD267、SD201 表現在線蟲的pharynx,並比較不同
基因型的SDAg,以及在不同發育階段表現SDAg 的結果有何差異,
藉以研究此蛋白對線蟲的影響。發現 (1) 除了SD201 此不具
nuclear-localization signal ( NLS )的SDAg 外,其餘的對線蟲有顯著影
響,(2) 在線蟲L4 時於pharynx 表現SDAg 會對線蟲造成最大影響,
(3) 對線蟲造成影響的強弱為:第二基因型大於第一基因型大於第三
基因型。以上結果顯示SDAg 需進入核內干擾核內未知分子作用才能
對線蟲造成影響。未來若能找到此分子,則可回推是否在人類也有同
源基因,而有助了解HDV 引起症狀的真相。
It is known that hepatitis delta virus (HDV) requires hepatitis B
virus (HBV) to complete its life cycle. When patients are coinfected or
superinfected with HBV and HDV, it causes fulminant hepatitis and
progressive chronic liver cirrhosis, indicating HDV plays an important
role that makes the symptoms become more seriously. The mechanism by
which HDV infection contributes to clinical hepatitis is poorly
understood. HDV has two different size of proteins, small and large delta
antigens (SDAg and LDAg), they might interact with hosts’ molecules
and make some symptoms. Our lab has established Caenorhabditis
elegans (C.elegans) as a platform to study whether HDV antigens will
affect worm growth. In previous studies, transgenic worms expressing
SDAg in pharynx caused growth retard. In my thesis, I used different
length of SDAgs named SD441, SD327, SD267, and SD201 to dissect
the domain of delta antigens, which leads to growth retard, as well the
effect of different genotypes (genotype I, genotype II, genotype III) and
expression at different stages. I found that (1) the influence are distinct in
all different length of SDAgs, except SD441, the SDAg without
nuclear-localization signal ( NLS ), (2) SDAg expression at L4 stage has
the most serious effect, and (3) the degree of effect is genotype II >
genotype I > genotype III. These results show that the entrance of SDAg
into hosts’ nucleus is very important to result in growth retardation and
egg-laying activity. SDAg might interfere with unknown molecules in the
nucleus. Therefore, if these molecules would be identified, we could
search for the homologous genes in human, and possible to delineate the
molecular mechanisms involved in the pathogenesis of HDV.
誌謝.............................................................................................................i
中文摘要....................................................................................................ii
Abstract.....................................................................................................iii
目錄...........................................................................................................iv
前言............................................................................................................1
實驗目的..................................................................................................10
材料與方法..............................................................................................11
實驗結果..................................................................................................25
討論..........................................................................................................34
參考文獻..................................................................................................39
圖..............................................................................................................46
附錄..........................................................................................................56
Abou-Jaoude, G. and C. Sureau (2007). "Entry of hepatitis delta virus
requires the conserved cysteine residues of the hepatitis B virus
envelope protein antigenic loop and is blocked by inhibitors of
thiol-disulfide exchange." J Virol 81(23): 13057-66.
Ameres, S. L., D. Shcherbakov, et al. (2007). "RNA chaperone activity of
L1 ribosomal proteins: phylogenetic conservation and splicing
inhibition." Nucleic Acids Res 35(11): 3752-63.
Bacaj, T. and S. Shaham (2007). "Temporal control of cell-specific
transgene expression in Caenorhabditis elegans." Genetics 176(4):
2651-5.
Bargmann, C. I. (2001). "High-throughput reverse genetics: RNAi
screens in Caenorhabditis elegans." Genome Biol 2(2):
REVIEWS1005.
Bell, P., R. Brazas, et al. (2000). "Hepatitis delta virus replication
generates complexes of large hepatitis delta antigen and antigenomic
RNA that affiliate with and alter nuclear domain 10." J Virol 74(11):
5329-36.
Blumenthal, T. (2004). "Operons in eukaryotes." Brief Funct Genomic
Proteomic 3(3): 199-211.
Bonino, F., K. H. Heermann, et al. (1986). "Hepatitis delta virus: protein
composition of delta antigen and its hepatitis B virus-derived
envelope." J Virol 58(3): 945-50.
Bracht, J., S. Hunter, et al. (2004). "Trans-splicing and polyadenylation of
let-7 microRNA primary transcripts." RNA 10(10): 1586-94.
40
Branch, A. D. and H. D. Robertson (1984). "A replication cycle for
viroids and other small infectious RNA's." Science 223(4635):
450-5.
Brazas, R. and D. Ganem (1996). "A cellular homolog of hepatitis delta
antigen: implications for viral replication and evolution." Science
274(5284): 90-4.
Brenner, S. (1974). "The genetics of Caenorhabditis elegans." Genetics
77(1): 71-94.
Casey, J. L., K. F. Bergmann, et al. (1992). "Structural requirements for
RNA editing in hepatitis delta virus: evidence for a
uridine-to-cytidine editing mechanism." Proc Natl Acad Sci U S A
89(15): 7149-53.
Casey, J. L. and J. L. Gerin (1995). "Hepatitis D virus RNA editing:
specific modification of adenosine in the antigenomic RNA." J Virol
69(12): 7593-600.
Chang, M. F., S. C. Baker, et al. (1988). "Human hepatitis delta antigen is
a nuclear phosphoprotein with RNA-binding activity." J Virol 62(7):
2403-10.
Chang, M. F., S. C. Chang, et al. (1992). "Nuclear localization signals,
but not putative leucine zipper motifs, are essential for nuclear
transport of hepatitis delta antigen." J Virol 66(10): 6019-27.
Chang, M. F., C. Y. Sun, et al. (1993). "Functional motifs of delta antigen
essential for RNA binding and replication of hepatitis delta virus." J
Virol 67(5): 2529-36.
Chao, M., S. Y. Hsieh, et al. (1990). "Role of two forms of hepatitis delta
41
virus antigen: evidence for a mechanism of self-limiting genome
replication." J Virol 64(10): 5066-9.
Chao, M., S. Y. Hsieh, et al. (1990). "Role of two forms of hepatitis delta
virus antigen: evidence for a mechanism of self-limiting genome
replication." J Virol 64(10): 5066-9.
Chao, M., S. Y. Hsieh, et al. (1991). "The antigen of hepatitis delta virus:
examination of in vitro RNA-binding specificity." J Virol 65(8):
4057-62.
Consortium, T. C. e. S. (1998). "Genome sequence of the nematode C.
elegans: a platform for investigating biology." Science 282(5396):
2012-8.
Evans, D. and T. Blumenthal (2000). "trans splicing of polycistronic
Caenorhabditis elegans pre-mRNAs: analysis of the SL2 RNA." Mol
Cell Biol 20(18): 6659-67.
Ganot, P., T. Kallesoe, et al. (2004). "Spliced-leader RNA trans splicing in
a chordate, Oikopleura dioica, with a compact genome." Mol Cell
Biol 24(17): 7795-805.
Guilhot, S., S. N. Huang, et al. (1994). "Expression of the hepatitis delta
virus large and small antigens in transgenic mice." J Virol 68(2):
1052-8.
Guiliano, D. B. and M. L. Blaxter (2006). "Operon conservation and the
evolution of trans-splicing in the phylum Nematoda." PLoS Genet
2(11): e198.
Haussecker, D., D. Cao, et al. (2008). "Capped small RNAs and MOV10
in human hepatitis delta virus replication." Nat Struct Mol Biol 15(7):
42
714-21.
Hobert, O. and P. Loria (2006). "Uses of GFP in Caenorhabditis elegans."
Methods Biochem Anal 47: 203-26.
Huang, C., S. C. Chang, et al. (2007). "Large hepatitis delta antigen is a
novel clathrin adaptor-like protein." J Virol 81(11): 5985-94.
Huang, I. C., C. Y. Chien, et al. (2006). "Induction of hepatitis D virus
large antigen translocation to the cytoplasm by hepatitis B virus
surface antigens correlates with endoplasmic reticulum stress and
NF-kappaB activation." J Gen Virol 87(Pt 6): 1715-23.
Huang, T., S. Kuersten, et al. (2001). "Intercistronic region required for
polycistronic pre-mRNA processing in Caenorhabditis elegans." Mol
Cell Biol 21(4): 1111-20.
Huang, W. H., C. W. Chen, et al. (2006). "Post-translational modification
of delta antigen of hepatitis D virus." Curr Top Microbiol Immunol
307: 91-112.
Huang, W. H., R. T. Mai, et al. (2008). "Transcription factor YY1 and its
associated acetyltransferases CBP and p300 interact with hepatitis
delta antigens and modulate hepatitis delta virus RNA replication." J
Virol 82(15): 7313-24.
Lai, M. M. (1995). "The molecular biology of hepatitis delta virus." Annu
Rev Biochem 64: 259-86.
Lazinski, D. W. and J. M. Taylor (1993). "Relating structure to function in
the hepatitis delta virus antigen." J Virol 67(5): 2672-80.
Lee, C. Z., P. J. Chen, et al. (1995). "Large hepatitis delta antigen in
packaging and replication inhibition: role of the carboxyl-terminal
43
19 amino acids and amino-terminal sequences." J Virol 69(9):
5332-6.
Lee, C. Z., J. H. Lin, et al. (1993). "RNA-binding activity of hepatitis
delta antigen involves two arginine-rich motifs and is required for
hepatitis delta virus RNA replication." J Virol 67(4): 2221-7.
Lin, J. H., M. F. Chang, et al. (1990). "Characterization of hepatitis delta
antigen: specific binding to hepatitis delta virus RNA." J Virol 64(9):
4051-8.
Longman, D., I. L. Johnstone, et al. (2000). "Functional characterization
of SR and SR-related genes in Caenorhabditis elegans." EMBO J
19(7): 1625-37.
Lu, R., M. Maduro, et al. (2005). "Animal virus replication and
RNAi-mediated antiviral silencing in Caenorhabditis elegans."
Nature 436(7053): 1040-3.
Macnaughton, T. B. and M. M. Lai (2002). "Genomic but not
antigenomic hepatitis delta virus RNA is preferentially exported
from the nucleus immediately after synthesis and processing." J
Virol 76(8): 3928-35.
Mello, C. and A. Fire (1995). "DNA transformation." Methods Cell Biol
48: 451-82.
Mello, C. C., J. M. Kramer, et al. (1991). "Efficient gene transfer in
C.elegans: extrachromosomal maintenance and integration of
transforming sequences." EMBO J 10(12): 3959-70.
Mello, C. C., J. M. Kramer, et al. (1991). "Efficient gene transfer in
C.elegans: extrachromosomal maintenance and integration of
44
transforming sequences." EMBO J 10(12): 3959-70.
Menne, S. and P. J. Cote (2007). "The woodchuck as an animal model for
pathogenesis and therapy of chronic hepatitis B virus infection."
World J Gastroenterol 13(1): 104-24.
Reece-Hoyes, J. S., J. Shingles, et al. (2007). "Insight into transcription
factor gene duplication from Caenorhabditis elegans
Promoterome-driven expression patterns." BMC Genomics 8: 27.
Shih, H. H., K. S. Jeng, et al. (2008). "Hepatitis B surface antigen levels
and sequences of natural hepatitis B virus variants influence the
assembly and secretion of hepatitis d virus." J Virol 82(5): 2250-64.
Shimozono, S., T. Fukano, et al. (2004). "Slow Ca2+ dynamics in
pharyngeal muscles in Caenorhabditis elegans during fast pumping."
EMBO Rep 5(5): 521-6.
Stein, L. D., Z. Bao, et al. (2003). "The genome sequence of
Caenorhabditis briggsae: a platform for comparative genomics."
PLoS Biol 1(2): E45.
Sureau, C. (2006). "The role of the HBV envelope proteins in the HDV
replication cycle." Curr Top Microbiol Immunol 307: 113-31.
Sureau, C., A. M. Moriarty, et al. (1992). "Production of infectious
hepatitis delta virus in vitro and neutralization with antibodies
directed against hepatitis B virus pre-S antigens." J Virol 66(2):
1241-5.
Tan, M. W. and F. M. Ausubel (2000). "Caenorhabditis elegans: a model
genetic host to study Pseudomonas aeruginosa pathogenesis." Curr
Opin Microbiol 3(1): 29-34.
45
Taylor, J. M. (2006). "Hepatitis delta virus." Virology 344(1): 71-6.
Vella, M. C., E. Y. Choi, et al. (2004). "The C. elegans microRNA let-7
binds to imperfect let-7 complementary sites from the lin-41
3'UTR." Genes Dev 18(2): 132-7.
Wei, C., P. Lamesch, et al. (2005). "Closing in on the C. elegans
ORFeome by cloning TWINSCAN predictions." Genome Res 15(4):
577-82.
Wilkins, C., R. Dishongh, et al. (2005). "RNA interference is an antiviral
defence mechanism in Caenorhabditis elegans." Nature 436(7053):
1044-7.
Wilson, R. K. (1999). "How the worm was won. The C. elegans genome
sequencing project." Trends Genet 15(2): 51-8.
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