長久以來人類一直與自然界中的病原體對抗，尤其是感染人類的病毒，許多與人類疾病相關的病毒能夠游走在急性和持續性感染之間，病毒一旦進入持續性感染後，便會潛藏在宿主中伺機而動，待宿主體內免疫系統降低，這些潛伏的病毒又會再次復發，往往患者會受到病毒反覆感染，造成醫療上的困擾，病人身心上的痛苦，因此，研究病毒持續性感染的機制是一項重要的課題。
Hz-1病毒是雙股DNA昆蟲病毒，基因組總長228 kb左右，是目前數種已完全定序完成的昆蟲病毒之一，其基因組中經預測大於50個胺基酸長度的開放讀架區(ORF)共有154個，另外，由過去的研究知道Hz-1病毒中有一段能轉錄成RNA而不產生蛋白的序列pag1存在，此段RNA是目前在Hz-1病毒進入持續感染期間唯一偵測到的病毒表現，Hz-1病毒是一個良好的模式病毒，一方面因為Hz-1病毒是昆蟲病毒，不會感染研究者；另一方面持續性感染的昆蟲細胞株已經存在，對於持續性感染機制的研究有很大的助益。因此，本篇論文便以Hz-1病毒為研究材料，藉著生物晶片技術的快速分析性與高精確性等優點，迅速分析Hz-1病毒基因間相互關係與在急性和持續性感染過程中的基因表現差異點，為了印證晶片分析結果，我們使用反轉錄聚合鏈反應。
為了達到實驗目標，首先我們建立了Hz-1病毒急性感染後0到24小時間基因表現圖譜(gene expression profiles)，另外，病毒進入持續性感染期時的基因表現圖譜也同時完成。隨後，將急性與持續性感染的基因表現圖譜，分別利用GeneSpring 6.0套裝分析軟體分析數據，過去的研究告訴我們，一些功能相似的病毒基因會在相近的時間點表現且也具有相同或相似的表現趨勢，依據此結果我們使用gene tree分析工具將急性感染過程中表現趨勢不同的病毒基因進行分群可歸成六大類(A-F)。 A群為在感染後持續表現至8小時後下降，此組中共有4個均無註解，一般此種感染後立即表現的基因，常是一些調控因子以控制宿主細胞，創造適合病毒複製適當的環境；B群為感染後出現兩次表現高峰，第一次出現在4小時表現較低量，第二次出現在20小時表現較高，群中共有22個ORFs有三個註解，IAP是抑制宿主細胞進行細胞自戕，可能此群中有些是幫助病毒控制宿主的因子；C群共有27個，表現在4或8小時出現高峰，而在16-24小時間表現持續高昇，此群中包含protein kinase及p34等調控因子；D群表現也是出現雙坡峰的表現型態，跟B群不同的是第一次在4小時且表現量較微弱，第二次出現在20小時共有26個；E群的特點是出現持續性高量表現在8-20小時，共有55個，此群中有許多與DNA複製相關的基因表現，如Shymidylate synthase (TS), Ribonucleotide reductase 1 (RR1) and RR2，及複製過程中所需的代謝因子；最後F群大部分在12-24小時有高表現，包含VLF-1基因存在。基因樹狀圖的分析有助於我們更了解Hz-1病毒基因間相互的關聯性，可以提供未來近一步研究的資訊。再則，持續性感染的基因圖譜藉由GeneSpring 6.0的分析我們發現表現大於兩倍的ORFs共有33個，在這些基因中，有許多基因與宿主細胞有同源關係，如 Thymidylate synthase (TS), Matrix metalloproteinase, Deoxynucleoside kinase, Ribonucleotide reductase 2 (RR2) 及 dUTP Pyrophosphatase, 也許這些基因的表現可能與病毒建立持續性感染有關。

Many viruses can infect their hosts as both productive and persistent infections. Persistently infected viruses can be reactivated when the host surveillance is decreased. It is an important issue to study the mechanism of the viral persistence. Hz-1 virus is a good model virus for that it is an insect virus and cannot infect human being. In addition, Hz-1 virus can establish persistently infected cell lines. Thus, Hz-1 virus is a very useful model virus for the study of persistent infection.
This proposal was to study the kinetics of gene expressions of Hz-1 virus during productive and persistent infections and to study the possible functions of these genes. Therefore, biochip technology was applied to establish Hz-1 viral gene expression profile during productive and persistent infections. Genes with similar functions have the same expression patterns. Using cluster analysis, all productively expressed genes were classified into six groups according to their similar expression patterns. Comparing genes with known function to those with unknown functions, the possible functions of these unknown genes were assigned. In addition, all Hz-1 viral ORFs that expressed during the persistent infection could be divided into six groups. The expression profiles of the Hz-1 virus during its productive and persistent infections were confirmed with RT-PCR and northern blot analyses.

王權輝，2003，Hz-1病毒DNA聚合脢基因表現模式、蛋白質純化與活化分析。國立成功大學生物科技研究所論文。

Aizaki, H., Harada, T., Otsuka, M., Seki, N., Matsuda, M., Li, Y. W., Kawakami, H., Matsuura, Y., Miyamura, T., and Suzuki, T. 2002. Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame. Hepatology 36: 1431-1438.

Alexandre, I., Hamels, S., Dufour, S., Collet, J., Zammatteo, N., De Longueville, F., Gala, J. L., and Remacle, J. 2001. Colorimetric silver detection of DNA microarrays. Anal Biochem 295: 1-8.

Bigger, C. B., Brasky, K. M., and Lanford, R. E. 2001. DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection. J Virol 75: 7059-7066.

Burand, J. P., Wood, H. A., and Summers, M. D. 1983. Defective particles from a persistent baculovirus infection in Trichoplusia ni tissue culture cells. J virol 64: 391-398.

Burand, J. P., Stiles, B., and Wood, H. A. 1983. Structural and intracellular proteins of the nonoccluded baculovirus Hz-1. J Virol 46: 137-142.

Chao, Y. C., Lee, S. T., Chang, M. C., Chen, H. H., Chen, S. S., Wu, T. Y., Liu, F. H., Hsu, E. L., and Hou, R. F. 1998. A 2.9-kilobase noncoding nuclear RNA functions in the establishment of persistent Hz-1 viral infection. J Virol 72: 2233-2245.

Chao, Y. C., Wood, H. A., Chang, C. Y., Lee, H. J., Shen, W. C., and Lee, H. T. 1992. Differential expression of Hz-1 baculovirus genes during productive and persistent viral infections. J Virol 66: 1442-1448.

Chao, Y. C., and Wood, H. A. 1990. The physical map of Hz-1 viral genome from standard and defective inference viral particles. J virol 71: 1265-1270.

Chen, H. H., Tsai, F. Y., and Chen, C. T. 2001a. Negative regulatory regions of the PAT1 promoter of Hz-1 virus contain GATA elements which associate with cellular factors and regulate promoter activity. J Gen Virol 82: 313-320.

Chen, H. H., Tso, D. J., Yeh, W. B., Cheng, H. J., and Wu, T. F. 2001b. The thymidylate synthase gene of Hz-1 virus: a gene captured from its lepidopteran host. Insect Mol Biol 10: 495-503.

Cheng, C. H., Liu, S. M., Chow, T. Y., Hsiao, Y. Y., Wang, D. P., Huang, J. J., and Chen, H. H. 2002. Analysis of the complete genome sequence of the Hz-1 virus suggests that it is related to members of the Baculoviridae. J Virol 76: 9024-9034.

Friesen, P. D., and Miller, L. K. 1986. The regulation of baculovirus gene expression. "The molecular biology of baculovirus" Doerfler, W. and P. Boehm. pp31-501. Spronger-Verlag, Berlin.
Guttieri, M. C., and Buran, J. P. 2001. Location, nucleotide sequence, and regulation of the p51 late gene of the hz-1 insect virus: identification of a putative late regulatory element. Virus Genes 23: 17-25.

Guttieri, M. C., and Burand, J. P. 1996. Nucleotide sequence, temporal expression, and transcriptional mapping of the p34 late gene of the Hz-1 insect virus. Virology 223: 370-375.

Harrap, K. 1972. The structure of nuclear polyhedrosis viruses. Virology 50: 114-123.

Hill, J. M., Lukiw, W. J., Gebhardt, B. M., Higaki, S., Loutsch, J. M., Myles, M. E., Thompson, H. W., Kwon, B. S., Bazan, N. G., and Kaufman, H. E. 2001. Gene expression analyzed by microarrays in HSV-1 latent mouse trigeminal ganglion following heat stress. Virus Genes 23: 273-280.

Ignoffo, C. M., Shapior, M., and Hink.,W. F. 1971. Replication and serial passage of infectious Heliothis nuclear polyhydrosis virus in an established line of Heliothis zea cells. Journal of invertebrate 18:131.

Iorio, C., Vialard, J. E., McCracken, S., Lagace, M., Richardson, C. D. 1998. The late expression factors 8 and 9 and possibly the phosphoprotein p78/83 of Autographa californica multicapsid nucleopolyhedrovirus are components of the virus-induced RNA polymerase. Intervirology 41: 35-46.

Lee, J. C., and Chao, Y. C. 1998. Apoptosis resulting from superinfection of Heliothis zea virus 1 is inhibited by p35 and is not required for virus interference. J Gen Virol 79: 2293-2300.

Lee, S. T., Yu, S. M., Hsu, E. L., and Chao, Y. C. 1995. Identification of a very early promoter of insect Hz-1 virus using a novel dual-expression shuttle vector. Nucleic Acids Res 23: 4683-4689.

Lee, J. C., Chen, H. H., Wei, H. L., and Chao, Y. C. 1993. Superinfection-induced apoptosis and its correlation with the reduction of viral progeny in cells persistently infected with Hz-1 baculovirus. J Virol 67: 6989-6994.

Li, J., Chen, S., and Evans, D. H. 2001. Typing and subtyping influenza virus using DNA microarrays and multiplex reverse transcriptase PCR. J Clin Microbiol 39: 696-704.

Lin, C. L., Lee, J. C., Chen, S. S., Wood, H. A., Li, M. L., Li, C. F., and Chao, Y. C. 1999. Persistent Hz-1 virus infection in insect cells: evidence for insertion of viral DNA into host chromosomes and viral infection in a latent status. J Virol 73: 128-139.

Meiners, S., Hocher, B., Weller, A., Laule, M., Stangl, V., Guenther, C., Godes, M., Mrozikiewicz, A., Baumann, G., Stangl, K. 2004. Downregulation of Matrix Metalloproteinases and Collagens and Suppression of Cardiac Fibrosis by Inhibition of the Proteasome. Hypertension 44: 1-7.

Okabe, H., Satoh, S., Kato, T., Kitahara, O., Yanagawa, R., Yamaoka, Y., Tsunoda, T., Furukawa, Y., and Nakamura, Y. 2001. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res 61: 2129-2137.

Richard, G. J., M. Mar Alba, Chris Boshoff, and Paul Kellam 2001. Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J virol 75: 891-902.

Smith, G. E. 1982. DNA homology among subgroup A, B, C bacul;ovirus. virology 123: 393-406.

Stingley, S. W., Ramirez, J. J., Aguilar, S. A., Simmen, K., Sandri-Goldin, R. M., Ghazal, P., and Wagner, E. K. 2000. Global analysis of herpes simplex virus type 1 transcription using an oligonucleotide-based DNA microarray. J Virol 74: 9916-9927.

Summers, M., Kawanishi, C. 1978. Viral pesticides: Present knowledge and potential effect on public and environment health. EPA Pub., Research Triangle Park, NC.

Summers, M., and Anderson, D. 1972. Granulosis virus deoxyribo-nucleic acid: a closed double-stranded molecule J virol 9: 710-713.

Tweeten, K. A., Bulla, L.A., and Consigli, R. A. 1980. Characyerization of an extremely basic protein derived from granulosis viral nucleocapsids. J virol 33: 866-876.

Volkman, L. E. 1995. Virus Taxonomy: The classification and nomenclature of viruses. In sixth report of the international Committee on Taxonomy of viruses. Archives of virology, Supplementum 3. Spring-Verlag, Wien, Inc., New York.

Wilson, M., 1991. Baculoviridae. In”Archives of virology supplementum2: Classification and nomenclature of virus” (Francki, R. I. B., C. M. Fauquent, D. C. Knudson, and F. Brown, Eds)pp117-123. Springer-Verlag, New York.

Wood, H. A., and Burand, J. P. 1986. Persistent and productive infections with the Hz-1 baculovirus. Curr Top Microbiol Immunol 131: 119-133.

Zangemeister Wittke U., Simon., H. U. 2004. An IAP in Action: The Multiple Roles of Survivin in Differentiation, Immunity and Malignancy. Cell Cycle 3: 3-9

Zammatteo, N., Jeanmart, L., Hamels, S., Courtois, S., Louette, P., Hevesi, L., and Remacle, J. 2000. Comparison between different strategies of covalent attachment of DNA to glass surfaces to build DNA microarrays. Anal Biochem 280: 143-150.