Graduate Institute of Clinical Medical Sciences

Lab

Research interests

The mature virion of EBV contains 6 capsid proteins, 10 viral glycoproteins, at least 17 viral-encoded tegument proteins. The formation of mature virion involves complex interactions among the capsid, tegument and glycoproteins, and is temporal-spatially and sequentially regulated. However, it is mostly unknown in the Epstein-Barr virus due to the lack of a permissive cell culture system for lytic infection. Our study revealed that BGLF2 and BBLF1 are critical to virion maturation. BGLF2 regulates virion maturation sequentially, which interacts with capsids and functions as an instructor, directing the nucleocapsid to TGN for final envelopment through the interaction with TGN-localized BBLF1 (Figure)

Our study currently revealed BGLF2 associated with at least 16 viral tegument or capsid proteins from the proteomic study. The ongoing study is focusing on these interactions with BLGF2 and the contribution to EBV virion maturation. BGLF2 influences cellular signaling pathways, such as activation of the MAPK pathway, cell cycle arrest at the G1 phase, and inhibition of anti-viral interferon signaling, to promote EBV infection. In addition, our proteomic study revealed BGLF2 associates with cellular proteins involved in the translation pathway, DNA repair, anti-viral response, trafficking, and proteolysis. The importance of BGLF2 interactome in EBV maturation, EBV lytic cycle regulation, and EBV pathogenesis are currently investigated. Our study will provide a better understanding of EBV pathogenesis and therapeutic targets for EBV associated diseases.

Publication

1. Li-Yu Chen, Lee-Wen Chen, Kuo-Ti Peng, Chien-Hui Hung, Pey-Jium Chang, Shie-Shan Wang. (2020) Sp3 Transcription factor cooperates with the Kaposi’s Sarcoma-associated herpesvirus ORF50 protein to synergistically activate specific viral and cellular gene promoters. Journal of Virology 94: e01143-20 (IF: 4.324, 8/36=22.8% Virology)
2. Tsung-Yu Huang, Kuo-Ti Peng, Wei-Hsiu Hsu, Chien-Hui Hung, Fang-Yi Chuang, Yao-Hung Tsai. (2020) Independent predictors of mortality for Aeromonas Necrotizing Fasciitis of Limbs: An 18-year Retrospective study. Scientific Reports 10: 7716 (IF: 3.998)
3. Chein-Hui Hung, Ya-Fang Chiu, Wen-Hung Wang, Lee-Wen Chen, Pey-Jium Chang, Tsung-Yu Huang, Ying-Ju Lin, Wan-Ju Tsai, Chia-Ching Yang. (2020) Interaction between BGLF2 and BBLF1 is required for the efficient production of infectious Epstein-Barr virus particles. Frontiers in microbiology10: 3021. (IF: 4.259, 32/133 microbiology)
4. Ching-Chuan Hsien, Chien-Hui Hung, Meihua Chiang, Yu-Chin Tsai, Jie-Teng He. (2019) Hepatic stellate cells enhance liver cancer progression by inducing myeloid-derived suppressor cells through interleukin-6 signaling. International Journal of molecular Sciences. 20: E5079. (IF: 4.183, 78/298 Biochemistry & Molecular biology, 46/172, Chemistry, Multidisciplinary)
5. Tsung-Yu Huang, Chien-Hui Hung, Wei-Hsiu Hsu, Kuo-Ti Peng, Ming-Szu Hung, Li-Ju Lai, Hui-Hu Chung, Wan-Ling Tai, Yu-Pei Ku, Ting-Shu Wu. (2019) Genitourinary tuberculosis in Taiwan: A 15-year experience at a teaching hospital. Journal of Microbiology Immunology and Infection. 52, 312-319. (IF: 2.455, 84/133 Microbiology)
6. Tsung-Yu Huang, Chien-Hui Hung, Li-Ju Lai, Hui-Ju Chuang, Chien-Chen Wang, Pei-Tzu Lin, Wei-Hsiu Hsu. (2018). Implementation and outcomes of hospital-wide computerized antimicrobial approval system and on-the-spot education in a traumatic intensive care unit in Taiwan. Journal of Microbiology Immunology and Infection. 51:672-680. (IF: 2.455, 84/133 Microbiology)
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8. Lee-Wen Chen, Chien-Hui Hung, Shie-Shan Wang, Ju-Bei Yen, Ann-Chi Liu, Ya-Hui Hung, Pey-Jium Chang. (2018) Expression and regulation of the BKRF2, BKRF3, and BKRF4 genes of Epstein-Barr virus. Virus Research 256: 76-89.
9. Ju-Bei Yen, Ling-Hui Wei, Lee-Wen Chen, Li-Yu Chen, Chien-Hui Hung, Shie-Shan Wang, Pey-Jium Chang. (2018) Subcellular localization and functional characterization of GII.4 Norovirus-encoded NTPase. Journal of Virology. 92: e01824-17. (IF: 4.324, 8/36=22.8% Virology)
10. Pey-Jium Chang, Lee-Wen Chen, Li-Yu Chen, Chien-Hui Hung, Ying-Ju Shih, Shie-Shan Wang. (2017). Effects of the NEDD8-activating enzyme inhibitor MLN4924 on lytic reactivation of Kaposi’s sarcoma-associated herpesvirus. Journal of Virology 91 (19): e00505-17. (IF: 4.324, 8/36=22.8% Virology)
11. Ching-Chuan Hsieh, Chien-Hui Hung, Lina Lu, Shiguang Qian. (2015). Hepatic immune tolerance induced by hepatic stellate cells. World Journal of Gastroenterology 21(42): 11887-11892. (IF: 3.365, 27/79=34.1 Gastroenterology & Hepatology)
12. Jing-Lan Liu, Fen-Fen Chen, Shun-Fu Chang, Cheng-Nan Chen, Jrhau Lung, Cheng-Hsing Lo, Fang-Hui Lee, Ying-Chou Lu, Chien-Hui Hung*. (2015). Expression of Beclin Family proteins is associated with tumor progression in oral cancer. PLoS ONE 10(10): e0141308. (IF: 2.806, 15/64=23% Multidisciplinary Sciences)
13. Jow-Jyh Hwang, Ching-Chu Lo, Chien-Hung Lin, Hsu-Sheng Cheng, I-Wen Hung, Wan-Ju Tsai, Chien-Hui Hung*. (2015). Association between IPTA gene polymorphisms and hematological abnormalities in HCV-infected patients receiving combination therapy. Gut and liver 9(2): 214-223. (IF: 2.663, 46/79=58.2% Gastroenterology & Hepatology).
14. Chien-Hui Hung*, Lee-Wen Chen, Wen-Hung Wang, Pey-Jium Chang, Ya-Fang Chiu, Chen-Chia Hung, Ying-Ju Lin, Jieh-Yuan Liou, Wen-Ju Tsai, Chia-Ling Hung, and Shih-Tung Liu*. (2014). Regulation of autophagic activation by Rta of Epstein-Barr virus via the extracellular signal-regulated kinase pathway. Journal of Virology 88 (20):12133-12145. (IF: 4.663, 6/33=18.1% Virology)
15. Jing-Lan Liu, Fen-Fen Chen, Jrhau Lung, Cheng-Hsing Lo, Fang-Hui Lee, Ying-Chou Lu, and Chien-Hui Hung*. (2014). Prognostic Significance of p62/SQSTM1 Subcellular Localization and LC3B in Oral Squamous Cell Carcinoma. British Journal of Cancer 111:944-954. (IF 6.176, 32/217=14.7% Oncology).
16. Pey-Jium Chang*, Chien-Hui Hung, Shie-Shan Wang, Ping-Hsin Tsai, Ying-Ju Shih, Li-Yu Chen, Hsiao-Yun Huang, Ling-Huei Wei, Ju-Bei Yen, Chun-Liang Lin, and Lee-Wen Chen. (2014). Identification and characterization of two novel spliced genes located in the orf47-orf46-orf45 gene locus of Kaposi's sarcoma- associated herpesvirus. Journal of Virology 88 (17):10092-10109. (IF: 4.663, 6/33=18.1% Virology).
17. Ying-Ju Lin*, Chia-Yen Chen, Kuan-Teh Jeang, Xiang Liu, Jen-Hsien Wang, Chien-Hui Hung, Hsinyi Tsang, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Cheng-Wen Lin, Mao-Wang Ho, Wen-Kuei Chien, Jin-Hua Chen, Tsung-Jung Ho and Fuu-Jen Tsai. (2014). Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture. Cell and Bioscience 4:40. (IF: 3.294, 106/286=37% Biochemistry & Molecular Biology).
18. Ying-Ju Lin, Yu-Ching Lan, Chien-Hui Hung, Ting-Hsu Lin, Shao-Mei Huang, Chiu-Chu Liao, Cheng-Wen Lin, Chih-Ho Lai, Ni Tien, Xiang Liu, Mao-Wang Ho, Wen-Kuei Chien, Jin-Hua Chen, Jen-Hsien Wang, Fuu-Jen Tsai. (2013) Variants in ZNRD1 gene predict HIV-1 AIDS disease pregression in a Han Chinese population in Taiwan. PLoS ONE 8(7): e67572. (IF: 2.806, 15/64=23% Multidisciplinary Sciences)
19. Ying-Ju Lin, Chine-Chen Lai, Chih-Ho Lai, Shih-Che Sue, Cheng-Wen Lin, Chien-Hui Hung, Ting-Shu Lin, Wei-Yi Hsu, Shao-Mei Huang, Yi-Lin Hung, Ni Tien, Xiang Liu, Chao-Ling Chen, Fuu-Jen Tsai. (2013) Inhibition of enterovirus 71 infections and viral IRES activity by Fructur gardeniae and geniposide. European Journal of Medicinal Chemistry 62:206-213. (IF: 4.519, 4/60=6.7% Chemistry, Medicinal)
20. Ya-Fang Chiu, Bill Sugden, Pey-Jium Chang, Lee-Wen Chen, Ying-Ju Lin, Yu-Ching Lan, Chih-Ho Lai, Jieh-Yuan Liou, Shih-Tung Liu, Chien-Hui Hung*. (2012) Characterization and intracellular trafficking of Epstein-Barr virus BBLF1, a protein involved in virion maturation. Journal of Virology 86:9647-9655 (IF: 4.663, 6/33=18.1% Virology).