臺灣博碩士論文加值系統

登革病毒(dengue virus，DENV)感染會引起登革熱(dengue fever，DF)、登革出血熱(dengue hemorrhagic fever，DHF)或登革休克症候群(dengue shock syndrome，DSS)，其高致病率及致死率已於世界各地造成嚴重健康威脅。茲卡病毒(zika virus，ZIKV)感染成人，輕微會造成短時間急性發燒，重則造成會危及生命的格林─巴利症候群(Guillain Barre Syndrome)及其他神經病變。目前也有越來越多的證據顯示茲卡病毒感染與初生兒小腦症(microcephaly)具有高度相關。然而，目前尚無任何有效的抗病毒藥物可用於對抗登革病毒及茲卡病毒引起的相關病症。我們以次世代定序分析細胞內受登革病毒調控之訊息RNA 表現，結果顯示肌醇多磷酸5端磷酸酶F(Inositol polyphosphate-5-phosphatase F，INPP5F)之訊息RNA隨著登革病毒感染時間延長而提高，此現象顯示INPP5F對於登革病毒複製的重要性。我們的實驗結果也證實隨著感染時間延長，登革病毒感染會誘導INPP5F的mRNA表現量，並且高度表現INPP5F可促進登革病毒複製。反之，利用shRNA抑制INPP5F則導致Akt/NF-κB調控之抗病毒干擾素反應活化而抑制登革病毒複製。此外，以adenovirus帶有之INPP5F shRNA抑制INPP5F表現則可保護受到致死性登革病毒感染之ICR乳鼠。綜合上述，誘導抗病毒干擾素反應或許可作為一有潛力之抗病毒藥物篩選目標。許多天然物曾被報導具有免疫調節效果，這些天然物或許也可作為抗病毒治療策略。因此我們挑選出一個五味子萃取物：五味子甲素 (schisandrin A)及一個酪梨萃取物：(2R,4R)-1,2,4-trihydroxyheptadec-16-yne (THHY)並檢驗其是否可以抑制登革病毒複製。結果顯示，隨著加藥劑量及加藥時間提高，schissandrin A及THHY可抑制四型登革病毒複製，且於有效濃度下無明顯細胞毒性。結果更顯示schisandrin A及THHY可有效保護受到登革病毒感染的ICR乳鼠免於嚴重症狀及死亡的威脅。此外我們也證明schisandrin A藉由調控STAT1/2活化抗病毒干擾素反應進而達到抑制登革病毒複製之效果。另一個天然物THHY也可隨著劑量提高抑制登革病毒複製，並且也可透過影響NF-κB調控之抗病毒干擾素反應有效抑制四型登革病毒複製。為了進一步延伸探討INPP5F對於類似黃病毒的生物活性，我們初步測試了INPP5F對於茲卡病毒(zika virus，ZIKV)之調控作用。茲卡病毒與登革病毒有許多類似特性，例如皆為依靠相同病媒蚊傳播、重疊的傳播區域、皆屬於黃病毒屬以及相似抗原性。有趣的是，我們發現抑制INPP5F同樣可有效抑制茲卡病毒複製。為了能進一步於活體中深入探討INPP5F對於茲卡病毒複製之影響，利用ICR乳鼠我們建立了一個可靠的茲卡病毒小動物模式。藉由收集並監控腦內注射及腹腔注射茲卡病毒的結果，我們能輕易得知動物的疾病狀況、神經症狀及死亡率。我們也進一步於肝臟、脾臟、腎臟及腦中也檢測到茲卡病毒存在。最後我們也利用一個茲卡病毒抑制劑Azithromycin (Az)來證明此茲卡感染動物模式的確可用。利用此動物模式，我們證明Az可抑制茲卡病毒感染導致之神經症狀及死亡。綜合以上結果，本研究證實了INPP5F藉由抑制Akt/NF-κB控制之抗病毒干擾素反應從而達到促進登革病毒複製之效果。我們也證實schisandrin A及THHY可有效抑制登革病毒複製。並且我們也建立了一個可靠的茲卡感染小動物模式，此動物模式可用於篩選抗茲卡病毒藥物及研究茲卡病毒複製之分子機轉及致病機轉。

Dengue virus (DENV) infection causes dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), leading to severe global health problem with substantial morbidity and mortality. Zika virus (ZIKV) infection caused diseases ranging from acute self-limiting febrile illness to life-threatening Guillain Barre Syndrome and other neurological disorders in adults. Cumulative evidence suggests an association between ZIKV infection and microcephaly in newborn infants. To date, there are still no FDA-approved drugs against DENV/ZIKV infection and the virus-related diseases. NGS analyses of cellular mRNAs that are modulated by DENV infection revealed the criticalness of elevated inositol polyphosphate-5-phosphatase F (INPP5F) mRNA levels upon DENV replication. Our results further demonstrated that INPP5F was induced by DENV infection in a time-dependent manner and overexpression of INPP5F enhanced DENV replication. In contrast, knockdown of INPP5F by shRNA resulted in the suppression of DENV-2 replication through induction of Akt/NF-κB-mediated antiviral interferon (IFN) responses. In addition, suppression of INPP5F by a recombinant adenovirus carrying INPP5F shRNA protected ICR suckling mice from life-threatened DENV-2 infection. Taken together, induction of antiviral IFN responses as a result of elevated INPP5F may be a potential strategy for anti-DENV development. As an alternative strategy, several natural products have been reported to exhibit immunoregulatory effect. We therefore selected a Schisandra chinensis extract schisandrin A and an avocado fruit extract (2R,4R)-1,2,4-trihydroxyheptadec-16-yne (THHY) to examine whether these natural products could suppress DENV-2 replication. Our results indicated that Schisandrin A and THHY inhibited all DENV serotypes (1–4) virus replication in a concentration- and time-dependent manner without significant cytotoxicity. Furthermore, schisandrin A and THHY effectively protected ICR suckling mice from DENV-2-caused severe disease symptoms and mortality in vivo. We also demonstrated that STAT1/2-mediated antiviral IFN responses contributes to the action of schisandrin A to against DENV-2 replication, while NF-κB-mediated antiviral IFN responses is induced by THHY to efficiently suppress replication of all DENV serotypes (1–4). To extend the biological effect of INPP5F on similar flaviviruses, we test the antiviral effect of INPP5F on zika virus (ZIKV) which has the common characteristics with DENV, including mosquito-borne transmission, overlapped epidemic areas, and similar genericity and antigenicity. Interestingly, suppression of INPP5F also effectively inhibited ZIKV replication. To further examine the inhibitory effect of INPP5F on ZIKV replication in vivo, we established a promising small animal model using ICR suckling mice for ZIKV infection. The signs of illness, neurological symptoms and mortality rate could be easily monitored from ICR mice that were intracerebrally or intraperitoneally injected with ZIKV. Viremic dissemination was observed in the liver, spleen, kidney, and brain. Using this mice model, we were also able to demonstrate that a ZIKV inhibitor Azithromycin (Az) confers protection against ZIKV-caused neurological and life-threatening diseases. In conclusion, our study indicated that INPP5F downregulated Akt/NF-B-mediated antiviral IFN responses to facilitate DENV replication. Natural products such as schisandrin A and THHY that enhance IFN responses are beneficial to suppress DENV infecton. Additionally, we established a promising ZIKV-infected small animal model, which can be conveniently used for screening drugs against ZIKV and investigating the underlying mechanism of ZIKV infection and pathogenesis.

中文摘要 .............. I
Abstract ............. III
誌謝 .............. V
目錄 ............... VII
圖表目錄 .............. X
INTRODUCTION ............. 1
1. Epidemiology and current therapy of DENV ...... 1
2. Genome organization of DENV .......... 1
3. Pathogenesis of DENV ........... 2
4. Inositol polyphosphate-5-phosphatase F ........ 3
5. Implication of NF-κB-mediated antiviral IFN responses on virus replication . 4
6. Introduction of Schisandra chinensis (Turcz.) Baill. ..... 5
7. Introduction of Persea americana Mill. ........ 6
8. Epidemiology and pathology of ZIKV ......... 6
9. Similarity and correlation between DENV and ZIKV ...... 8
10. DENV infection mouse model ......... 9
11. ZIKV infection mouse model .......... 10
12. Study goal .............. 11
MATERIALS AND METHODS .......... 13
1. Cells and virus ............ 13
2. Reagents .............. 13
3. Plasmid construction ............ 14
4. Next-generation sequencing (NGS) analysis of DENV infection .... 14
5. Western blotting analysis ........... 14
6. DENV, cellular, and mice mRNAs RNA quantification ..... 15
7. Transfection and luciferase activity assay........ 16
8. Measurement of viral titers ......... 16
9. Ethics statement and experimental animals ...... 17
10. Evaluation of protective effect of SA on DENV-infected ICR suckling mice . 17
11. Evaluation of protective effect of THHY on DENV-infected ICR suckling mice
......18
12. Plaque assay for determination of DENV titer ...... 19
13. Evaluation of protective effect of shINPP5F on DENV-infected ICR suckling mice
.......19
14. Evaluation of susceptibility of ICR suckling mice to ZIKV infection ... 20
15. Quantification of extracellular interferon alpha (IFN-α) ..... 21
16. Plaque assay for determination of DENV titer ...... 21
17. Quantitation of monocyte infiltration......... 21
18. Evaluation of anti-ZIKV replication activity assay in ICR suckling mouse model
.......22
RESULTS ............. 23
1. NGS analysis of DENV infection ......... 23
2. INPP5F enhances DENV replication in vitro ....... 23
3. INPP5F regulates NF-κB through mediating Akt activation ... 24
4. INPP5F suppresses antiviral IFN responses via down-regulating Akt and NF-κB
pathway activation ............. 24
5. Suppression of INPP5F protects ICR suckling mice from life-threatening DENV
infection .....25
6. Schisandrin A inhibits DENV RNA replication and protein synthesis ... 26
7. Schisandrin A decreases the mortality of DENV-infected ICR suckling mice27
8. Schisandrin A induces antiviral IFN-I gene expression .... 28
9. Schisandrin A increased STAT1/2 phosphorylation for induction of antiviral IFN
responses ............... 29
10. Schisandrin A inhibits DENV replication and stimulates IFN-mediated antiviral
responses in vivo ............. 30
11. Avocado extract THHY exhibits anti-DENV activity ..... 30
12. THHY inhibits DENV replication by NF-κB-mediated IFN production .. 31
13. THHY induces antiviral IFN responses through the STAT pathway ... 32
14. THHY protects ICR suckling mice against life-threatening DENV infection 33
15. Suppression of INPP5F inhibited ZIKV replication in vitro .... 33
16. ZIKV caused lethality in the suckling mouse model ..... 34
17. ZIKV replicated in ZIKV-infected ICR suckling mice ..... 35
18. ZIKV induced monocyte infiltrated into the brain of ICR suckling mice .. 36
19. ZIKV invaded brain tissue of ICR suckling mice ..... 37
20. Azithromycin prevented ZIKV-induced lethality and inhibited ZIKV replication in
the suckling mouse model ............ 37
DISCUSSION ............. 40
1. Clarification of INPP5F-mediated antiviral IFN pathway on DENV and ZIKV
replication ............... 40
2. Alternative targets of INPP5F on DENV and ZIKV replication ... 42
3. Possibility of NF-κB-mediated antiviral IFN responses served as anti-DENV/ZIKV
strategy .............. 44
4. Schisandrin A and THHY may efficiently inhibit ZIKV replication .. 46
5. Alternative targets of schisandrin A and THHY against DENV infection . 47
6. Establishment of ZIKV small animal model ...... 48
7. Development of a fast and easy-performing animal model .... 48
8. Impact of present results on investigating antiviral effect .... 49
Conclusion .............. 51
References .............. 52
Figure .............. 66
圖表目錄
Figure 1. NGS analysis of genes changes upon DENV infection. -- 66
Figure 2. Suppression of INPP5F inhibited DENV replication. --- 67
Figure 3. INPP5F mediated Akt-NF-κB activation to regulate DENV replication.
---------- 69
Figure 4. Suppression of INPP5F enhanced antiviral IFN expression level upon
DENV infection. --------- 71
Figure 5. INPP5F-mediated ISGs expression upon DENV replication was
contributed to DENV replication. ------- 72
Figure 6. Suppression of INPP5F protected suckling mice from life-threatened
DENV infection. --------- 74
Figure 7. Schisandrin A efficiently inhibits DENV replication in a dose-dependent
manner. ---------- 76
Figure 8. Cell viability of schisandrin A, schisandrin B, and schisandrin C. - 78
Figure 9. Schisandrin A inhibits replication of four serotypes of DENV. -- 79
Figure 10. Schisandrin A protects ICR suckling mice from DENV infection. 81
Figure 11. Schisandrin A induces antiviral IFN-α expression. --- 82
Figure 12. Schisandrin A increases cellular antiviral IFN-α expression in naïve
Huh-7 cells. --------- 83
Figure 13. Schisandrin A stimulates STAT1 and STAT2 phosphorylation. - 84
Figure 14. Schisandrin A induces ISRE activity and antiviral IFN response gene
expression. ---------- 85
Figure 15. Schisandrin A inhibits DENV replication in vivo through modulating
IFN-mediated antiviral responses. ------- 87
Figure 16. Avocado extract THHY exhibits anti-DENV effect in vitro. -- 89
Figure 17. THHY inhibits DENV replication via up-regulation of NF-κB activity.
---------- 91
Figure 18. THHY inhibits DENV replication via induction of antiviral IFN
production ---------- 93
Figure 19. THHY inhibits DENV replication by increasing STAT activity and
downstream antiviral gene expression. ----- 95
Figure 20. THHY protects ICR suckling mice against lethal DENV infection.97
Figure 21. Suppression of INPP5F inhibited ZIKV replication. --- 98
Figure 22. Survival rate, body weight, and clinical score of ICR suckling mice
infected with ZIKV by i.p. and i.c. injection. ---- 99
Figure 23. ZIKV replication in different organs of mice that underwent i.p. and i.c.
injection of various doses of ZIKV. ----- 101
Figure 24. Monocyte infiltration in the brain of ICR suckling mice that received i.c.
injection of various doses of ZIKV. ----- 104
Figure 25. ZIKV infection increases monocyte infiltration in mice brain tissues in a
dose-dependent manner. -------- 106
Figure 26. ZIKV replication in the brain of mice i.p. injected with 104 PFU ZIKV.
----------- 107
Figure 27. ZIKV infection increases monocyte infiltration in mice brain in a timedependent
manner. --------- 109
Figure 28. Survival rate, body weight, and clinical score in ZIKV-infected ICR
suckling mice treated with Az. ------- 110
Figure 29. ZIKV replication and ZIKV-induced monocyte infiltration were
suppressed by Az treatment in ZIKV-infected ICR suckling mice. -- 112
Figure 30. ZIKV-induced monocyte infiltration are suppressed by Az treatment in
ICR suckling mice. --------- 114
Appendix Index
Appendix 1. Oligonucleotide sequences for real-time RT-PCR. .. 115
Appendix 2. pNFκB-Luc ......... 117
Appendix 3. pISRE-Luc .......... 117
Appendix 4. pCMV-HA-INPP5F ........ 118
Appendix 5. pAd-shINPP5F ......... 118

Acosta, E. G., ＆ Bartenschlager, R. (2016). The quest for host targets to combat dengue virus infections. Curr Opin Virol, 20, 47-54.
Akinpelu, D. A., Aiyegoro, O. A., Akinpelu, O. F., ＆ Okoh, A. I. (2014). Stem bark extract and fraction of Persea americana (Mill.) exhibits bactericidal activities against strains of bacillus cereus associated with food poisoning. Molecules, 20(1), 416-429.
Al-Tawfiq, J. A., ＆ Memish, Z. A. (2018). Dengue Hemorrhagic Fever Virus in Saudi Arabia: A Review. Vector Borne Zoonotic Dis, 18(2), 75-81.
Alam, A., Imam, N., Farooqui, A., Ali, S., Malik, M. Z., ＆ Ishrat, R. (2017). Recent trends in ZikV research: A step away from cure. Biomed Pharmacother, 91, 1152-1159.
Albulescu, L., Wubbolts, R., van Kuppeveld, F. J., ＆ Strating, J. R. (2015). Cholesterol shuttling is important for RNA replication of coxsackievirus B3 and encephalomyocarditis virus. Cell Microbiol, 17(8), 1144-1156.
Aliota, M. T., Caine, E. A., Walker, E. C., Larkin, K. E., Camacho, E., ＆ Osorio, J. E. (2016). Characterization of Lethal Zika Virus Infection in AG129 Mice. PLoS Negl Trop Dis, 10(4), e0004682.
Andreakos, E., Sacre, S. M., Smith, C., Lundberg, A., Kiriakidis, S., Stonehouse, T., Monaco, C., Feldmann, M., ＆ Foxwell, B. M. (2004). Distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP. Blood, 103(6), 2229-2237.
Anusuya, S., Velmurugan, D., ＆ Gromiha, M. M. (2016). Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study. J Biomol Struct Dyn, 34(7), 1512-1532.
Arzuza-Ortega, L., Polo, A., Perez-Tatis, G., Lopez-Garcia, H., Parra, E., Pardo-Herrera, L. C., Rico-Turca, A. M., Villamil-Gomez, W., ＆ Rodriguez-Morales, A. J. (2016). Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia. Emerg Infect Dis, 22(5), 925-927.
Azizan, A., Sweat, J., Espino, C., Gemmer, J., Stark, L., ＆ Kazanis, D. (2006). Differential proinflammatory and angiogenesis-specific cytokine production in human pulmonary endothelial cells, HPMEC-ST1.6R infected with dengue-2 and dengue-3 virus. J Virol Methods, 138(1-2), 211-217.
Bai, D., Zhang, Y., Shen, M., Sun, Y., Xia, Q., Zhang, Y., Liu, X., Wang, H., ＆ Yuan, L. (2016). Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart. Sci Rep, 6, 22068.
Bardina, S. V., Bunduc, P., Tripathi, S., Duehr, J., Frere, J. J., Brown, J. A., Nachbagauer, R., Foster, G. A., Krysztof, D., Tortorella, D., Stramer, S. L., Garcia-Sastre, A., Krammer, F., ＆ Lim, J. K. (2017). Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science, 356(6334), 175-180.
Beatty, P. R., Puerta-Guardo, H., Killingbeck, S. S., Glasner, D. R., Hopkins, K., ＆ Harris, E. (2015). Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination. Sci Transl Med, 7(304), 304ra141.
Belov, G. A., ＆ van Kuppeveld, F. J. (2012). (+)RNA viruses rewire cellular pathways to build replication organelles. Curr Opin Virol, 2(6), 740-747.
Bishe, B., Syed, G. H., Field, S. J., ＆ Siddiqui, A. (2012). Role of phosphatidylinositol 4-phosphate (PI4P) and its binding protein GOLPH3 in hepatitis C virus secretion. J Biol Chem, 287(33), 27637-27647.
Brai, B. I., Adisa, R. A., ＆ Odetola, A. A. (2014). Hepatoprotective properties of aqueous leaf extract of Persea Americana, Mill (Lauraceae) 'avocado' against CCL4-induced damage in rats. Afr J Tradit Complement Altern Med, 11(2), 237-244.
Brasil, P., Sequeira, P. C., Freitas, A. D., Zogbi, H. E., Calvet, G. A., de Souza, R. V., Siqueira, A. M., de Mendonca, M. C., Nogueira, R. M., de Filippis, A. M., ＆ Solomon, T. (2016). Guillain-Barre syndrome associated with Zika virus infection. Lancet, 387(10026), 1482.
Cao-Lormeau, V. M., Blake, A., Mons, S., Lastere, S., Roche, C., Vanhomwegen, J., Dub, T., Baudouin, L., Teissier, A., Larre, P., Vial, A. L., Decam, C., Choumet, V., Halstead, S. K., Willison, H. J., Musset, L., Manuguerra, J. C., Despres, P., Fournier, E., Mallet, H. P., Musso, D., Fontanet, A., Neil, J., ＆ Ghawche, F. (2016). Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet, 387(10027), 1531-1539.
Cao-Lormeau, V. M., Roche, C., Teissier, A., Robin, E., Berry, A. L., Mallet, H. P., Sall, A. A., ＆ Musso, D. (2014). Zika virus, French polynesia, South pacific, 2013. Emerg Infect Dis, 20(6), 1085-1086.
Chan, J. F., Choi, G. K., Yip, C. C., Cheng, V. C., ＆ Yuen, K. Y. (2016). Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease. J Infect, 72(5), 507-524.
Chan, J. F., Yip, C. C., Tsang, J. O., Tee, K. M., Cai, J. P., Chik, K. K., Zhu, Z., Chan, C. C., Choi, G. K., Sridhar, S., Zhang, A. J., Lu, G., Chiu, K., Lo, A. C., Tsao, S. W., Kok, K. H., Jin, D. Y., Chan, K. H., ＆ Yuen, K. Y. (2016). Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. Emerg Microbes Infect, 5, e93.
Charles, A. S., ＆ Christofferson, R. C. (2016). Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro. PLoS Curr, 8.
Charlier, N., Leyssen, P., De Clercq, E., ＆ Neyts, J. (2004). Rodent models for the study of therapy against flavivirus infections. Antiviral Res, 63(2), 67-77.
Checker, R., Patwardhan, R. S., Sharma, D., Menon, J., Thoh, M., Bhilwade, H. N., Konishi, T., ＆ Sandur, S. K. (2012). Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-kappaB. Free Radic Biol Med, 53(7), 1421-1430.
Chen, H. W., King, K., Tu, J., Sanchez, M., Luster, A. D., ＆ Shresta, S. (2013). The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus. J Immunol, 191(8), 4194-4201.
Chen, Y., Wei, H., Liu, F., ＆ Guan, J. L. (2014). Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) promotes breast cancer progression through enhancing glucose starvation-induced autophagy and Akt signaling. J Biol Chem, 289(2), 1164-1173.
Cho, N. J., Lee, C., Pang, P. S., Pham, E. A., Fram, B., Nguyen, K., Xiong, A., Sklan, E. H., Elazar, M., Koytak, E. S., Kersten, C., Kanazawa, K. K., Frank, C. W., ＆ Glenn, J. S. (2015). Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A ligand and mediates replication of the viral genome. Gastroenterology, 148(3), 616-625.
Collins, S. E., ＆ Mossman, K. L. (2014). Danger, diversity and priming in innate antiviral immunity. Cytokine Growth Factor Rev, 25(5), 525-531.
Dejnirattisai, W., Supasa, P., Wongwiwat, W., Rouvinski, A., Barba-Spaeth, G., Duangchinda, T., Sakuntabhai, A., Cao-Lormeau, V. M., Malasit, P., Rey, F. A., Mongkolsapaya, J., ＆ Screaton, G. R. (2016). Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nat Immunol, 17(9), 1102-1108.
Diamond, M. S., Roberts, T. G., Edgil, D., Lu, B., Ernst, J., ＆ Harris, E. (2000). Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons. J Virol, 74(11), 4957-4966.
Diwaker, D., Mishra, K. P., Ganju, L., ＆ Singh, S. B. (2014). Rhodiola inhibits dengue virus multiplication by inducing innate immune response genes RIG-I, MDA5 and ISG in human monocytes. Arch Virol, 159(8), 1975-1986.
Dorobantu, C. M., Albulescu, L., Harak, C., Feng, Q., van Kampen, M., Strating, J. R., Gorbalenya, A. E., Lohmann, V., van der Schaar, H. M., ＆ van Kuppeveld, F. J. (2015). Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus. PLoS Pathog, 11(9), e1005185.
Dowall, S. D., Graham, V. A., Rayner, E., Atkinson, B., Hall, G., Watson, R. J., Bosworth, A., Bonney, L. C., Kitchen, S., ＆ Hewson, R. (2016). A Susceptible Mouse Model for Zika Virus Infection. PLoS Negl Trop Dis, 10(5), e0004658.
Duffy, M. R., Chen, T. H., Hancock, W. T., Powers, A. M., Kool, J. L., Lanciotti, R. S., Pretrick, M., Marfel, M., Holzbauer, S., Dubray, C., Guillaumot, L., Griggs, A., Bel, M., Lambert, A. J., Laven, J., Kosoy, O., Panella, A., Biggerstaff, B. J., Fischer, M., ＆ Hayes, E. B. (2009). Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med, 360(24), 2536-2543.
Duggal, N. K., Ritter, J. M., McDonald, E. M., Romo, H., Guirakhoo, F., Davis, B. S., Chang, G. J., ＆ Brault, A. C. (2017). Differential Neurovirulence of African and Asian Genotype Zika Virus Isolates in Outbred Immunocompetent Mice. Am J Trop Med Hyg, 97(5), 1410-1417.
Esmat, G., El Kassas, M., Hassany, M., Gamil, M., ＆ El Raziky, M. (2014). Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues. Liver Int, 34 Suppl 1, 24-28.
Esteves, E., Rosa, N., Correia, M. J., Arrais, J. P., ＆ Barros, M. (2017). New Targets for Zika Virus Determined by Human-Viral Interactomic: A Bioinformatics Approach. Biomed Res Int, 2017, 1734151.
Faye, O., Freire, C. C., Iamarino, A., Faye, O., de Oliveira, J. V., Diallo, M., Zanotto, P. M., ＆ Sall, A. A. (2014). Molecular evolution of Zika virus during its emergence in the 20(th) century. PLoS Negl Trop Dis, 8(1), e2636.
Fink, K., ＆ Grandvaux, N. (2013). STAT2 and IRF9: Beyond ISGF3. JAKSTAT, 2(4), e27521.
Fowler, A. M., Tang, W. W., Young, M. P., Mamidi, A., Viramontes, K. M., McCauley, M. D., Carlin, A. F., Schooley, R. T., Swanstrom, J., Baric, R. S., Govero, J., Diamond, M. S., ＆ Shresta, S. (2018). Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice. Cell Host Microbe, 24(5), 743-750 e745.
Grant, A., Ponia, S. S., Tripathi, S., Balasubramaniam, V., Miorin, L., Sourisseau, M., Schwarz, M. C., Sanchez-Seco, M. P., Evans, M. J., Best, S. M., ＆ Garcia-Sastre, A. (2016). Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling. Cell Host Microbe, 19(6), 882-890.
Green, A. M., Beatty, P. R., Hadjilaou, A., ＆ Harris, E. (2014). Innate immunity to dengue virus infection and subversion of antiviral responses. J Mol Biol, 426(6), 1148-1160.
Guo, L. Y., Hung, T. M., Bae, K. H., Shin, E. M., Zhou, H. Y., Hong, Y. N., Kang, S. S., Kim, H. P., ＆ Kim, Y. S. (2008). Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. Eur J Pharmacol, 591(1-3), 293-299.
Heaton, N. S., ＆ Randall, G. (2010). Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe, 8(5), 422-432.
Helin, E., Vainionpaa, R., Hyypia, T., Julkunen, I., ＆ Matikainen, S. (2001). Measles virus activates NF-kappa B and STAT transcription factors and production of IFN-alpha/beta and IL-6 in the human lung epithelial cell line A549. Virology, 290(1), 1-10.
Heymann, D. L., Hodgson, A., Sall, A. A., Freedman, D. O., Staples, J. E., Althabe, F., Baruah, K., Mahmud, G., Kandun, N., Vasconcelos, P. F., Bino, S., ＆ Menon, K. U. (2016). Zika virus and microcephaly: why is this situation a PHEIC? Lancet, 387(10020), 719-721.
Hiscott, J. (2007). Convergence of the NF-kappaB and IRF pathways in the regulation of the innate antiviral response. Cytokine Growth Factor Rev, 18(5-6), 483-490.
Hishiki, T., Han, Q., Arimoto, K., Shimotohno, K., Igarashi, T., Vasudevan, S. G., Suzuki, Y., ＆ Yamamoto, N. (2014). Interferon-mediated ISG15 conjugation restricts dengue virus 2 replication. Biochem Biophys Res Commun, 448(1), 95-100.
Horner, S. M. (2015). Insights into antiviral innate immunity revealed by studying hepatitis C virus. Cytokine, 74(2), 190-197.
Hsu, Y. C., Chen, N. C., Chen, P. C., Wang, C. C., Cheng, W. C., ＆ Wu, H. N. (2012). Identification of a small-molecule inhibitor of dengue virus using a replicon system. Arch Virol, 157(4), 681-688.
Hu, D., Li, C., Han, N., Miao, L., Wang, D., Liu, Z., Wang, H., ＆ Yin, J. (2012). Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Abeta(1)(-)(4)(2)-induced memory impairment in mice. Planta Med, 78(12), 1332-1336.
Huang, S. C., Chang, C. L., Wang, P. S., Tsai, Y., ＆ Liu, H. S. (2009). Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. J Med Virol, 81(7), 1241-1252.
Iannetta, M., Ippolito, G., ＆ Nicastri, E. (2017). Azithromycin Shows Anti-Zika Virus Activity in Human Glial Cells. Antimicrob Agents Chemother, 61(9).
Israeli, E., Agmon-Levin, N., Blank, M., Chapman, J., ＆ Shoenfeld, Y. (2012). Guillain-Barre syndrome--a classical autoimmune disease triggered by infection or vaccination. Clin Rev Allergy Immunol, 42(2), 121-130.
Jiang, D., Weidner, J. M., Qing, M., Pan, X. B., Guo, H., Xu, C., Zhang, X., Birk, A., Chang, J., Shi, P. Y., Block, T. M., ＆ Guo, J. T. (2010). Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections. J Virol, 84(16), 8332-8341.
Jones, M., Davidson, A., Hibbert, L., Gruenwald, P., Schlaak, J., Ball, S., Foster, G. R., ＆ Jacobs, M. (2005). Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. J Virol, 79(9), 5414-5420.
Kawiecki, A. B., ＆ Christofferson, R. C. (2016). Zika Virus-Induced Antibody Response Enhances Dengue Virus Serotype 2 Replication In Vitro. J Infect Dis, 214(9), 1357-1360.
Kim, H., Ahn, Y. T., Kim, Y. S., Cho, S. I., ＆ An, W. G. (2014). Antiasthmatic effects of schizandrae fructus extract in mice with asthma. Pharmacogn Mag, 10(Suppl 1), S80-85.
Kim, H. S., Li, A., Ahn, S., Song, H., ＆ Zhang, W. (2014). Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity. Sci Rep, 4, 7330.
Krishnan, M. N., ＆ Garcia-Blanco, M. A. (2014). Targeting host factors to treat West Nile and dengue viral infections. Viruses, 6(2), 683-708.
Kulkarni, P., Paul, R., ＆ Ganesh, N. (2010). In vitro evaluation of genotoxicity of avocado (Persea americana) fruit and leaf extracts in human peripheral lymphocytes. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 28(3), 172-187.
Kuno, G., ＆ Chang, G. J. (2007). Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol, 152(4), 687-696.
Kyle, J. L., ＆ Harris, E. (2008). Global spread and persistence of dengue. Annu Rev Microbiol, 62, 71-92.
Lazear, H. M., Govero, J., Smith, A. M., Platt, D. J., Fernandez, E., Miner, J. J., ＆ Diamond, M. S. (2016). A Mouse Model of Zika Virus Pathogenesis. Cell Host Microbe, 19(5), 720-730.
Lee, Y. R., Hu, H. Y., Kuo, S. H., Lei, H. Y., Lin, Y. S., Yeh, T. M., Liu, C. C., ＆ Liu, H. S. (2013). Dengue virus infection induces autophagy: an in vivo study. J Biomed Sci, 20, 65.
Lee, Y. R., Kuo, S. H., Lin, C. Y., Fu, P. J., Lin, Y. S., Yeh, T. M., ＆ Liu, H. S. (2018). Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo. Sci Rep, 8(1), 489.
Li, C., Xu, D., Ye, Q., Hong, S., Jiang, Y., Liu, X., Zhang, N., Shi, L., Qin, C. F., ＆ Xu, Z. (2016). Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. Cell Stem Cell, 19(1), 120-126.
Li, H., Saucedo-Cuevas, L., Regla-Nava, J. A., Chai, G., Sheets, N., Tang, W., Terskikh, A. V., Shresta, S., ＆ Gleeson, J. G. (2016). Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation. Cell Stem Cell, 19(5), 593-598.
Li, H., Yang, X., Yang, G., Hong, Z., Zhou, L., Yin, P., Xiao, Y., Chen, L., Chung, R. T., ＆ Zhang, L. (2014). Hepatitis C virus NS5A hijacks ARFGAP1 to maintain a phosphatidylinositol 4-phosphate-enriched microenvironment. J Virol, 88(11), 5956-5966.
Li, J., Wang, J., Shao, J. Q., Du, H., Wang, Y. T., ＆ Peng, L. (2015). Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise. Chin J Integr Med, 21(1), 43-48.
Li, S., Armstrong, N., Zhao, H., Hou, W., Liu, J., Chen, C., Wan, J., Wang, W., Zhong, C., Liu, C., Zhu, H., Xia, N., Cheng, T., ＆ Tang, Q. (2018). Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System. Viruses, 10(1).
Li, S., Labrecque, S., Gauzzi, M. C., Cuddihy, A. R., Wong, A. H., Pellegrini, S., Matlashewski, G. J., ＆ Koromilas, A. E. (1999). The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene, 18(42), 5727-5737.
Lim, S. P., Wang, Q. Y., Noble, C. G., Chen, Y. L., Dong, H., Zou, B., Yokokawa, F., Nilar, S., Smith, P., Beer, D., Lescar, J., ＆ Shi, P. Y. (2013). Ten years of dengue drug discovery: progress and prospects. Antiviral Res, 100(2), 500-519.
Lin, C. H., Schioler, K. L., Jepsen, M. R., Ho, C. K., Li, S. H., ＆ Konradsen, F. (2012). Dengue outbreaks in high-income area, Kaohsiung City, Taiwan, 2003-2009. Emerg Infect Dis, 18(10), 1603-1611.
Lin, C. K., Tseng, C. K., Wu, Y. H., Liaw, C. C., Lin, C. Y., Huang, C. H., Chen, Y. H., ＆ Lee, J. C. (2017). Cyclooxygenase-2 facilitates dengue virus replication and serves as a potential target for developing antiviral agents. Sci Rep, 7, 44701.
Lin, R., Heylbroeck, C., Pitha, P. M., ＆ Hiscott, J. (1998). Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol Cell Biol, 18(5), 2986-2996.
Lin, Y. T., Wu, Y. H., Tseng, C. K., Lin, C. K., Chen, W. C., Hsu, Y. C., ＆ Lee, J. C. (2013). Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation. PLoS One, 8(1), e54466.
Liu, H., Lai, H., Jia, X., Liu, J., Zhang, Z., Qi, Y., Zhang, J., Song, J., Wu, C., Zhang, B., ＆ Xiao, P. (2013). Comprehensive chemical analysis of Schisandra chinensis by HPLC-DAD-MS combined with chemometrics. Phytomedicine, 20(12), 1135-1143.
Liu, P., Woda, M., Ennis, F. A., ＆ Libraty, D. H. (2009). Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon effects. J Infect Dis, 200(2), 191-201.
Lu, Y. C., Chang, H. S., Peng, C. F., Lin, C. H., ＆ Chen, I. S. (2012). Secondary metabolites from the unripe pulp of Persea americana and their antimycobacterial activities. Food Chem, 135(4), 2904-2909.
Mackenzie, J. M., Khromykh, A. A., ＆ Parton, R. G. (2007). Cholesterol manipulation by West Nile virus perturbs the cellular immune response. Cell Host Microbe, 2(4), 229-239.
Maia, L. M. S., Bezerra, M. C. F., Costa, M. C. S., Souza, E. M., Oliveira, M. E. B., Ribeiro, A. L. M., Miyazaki, R. D., ＆ Slhessarenko, R. D. (2019). Natural vertical infection by dengue virus serotype 4, Zika virus and Mayaro virus in Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus. Med Vet Entomol.
Marrs, C., Olson, G., Saade, G., Hankins, G., Wen, T., Patel, J., ＆ Weaver, S. (2016). Zika Virus and Pregnancy: A Review of the Literature and Clinical Considerations. Am J Perinatol, 33(7), 625-639.
McBride, W. J., ＆ Bielefeldt-Ohmann, H. (2000). Dengue viral infections; pathogenesis and epidemiology. Microbes Infect, 2(9), 1041-1050.
Minagawa, T., Ijuin, T., Mochizuki, Y., ＆ Takenawa, T. (2001). Identification and characterization of a sac domain-containing phosphoinositide 5-phosphatase. J Biol Chem, 276(25), 22011-22015.
Miranda, M. M., Almeida, A. P., Costa, S. S., Santos, M. G., Lagrota, M. H., ＆ Wigg, M. D. (1997). In vitro activity of extracts of Persea americana leaves on acyclovir-resistant and phosphonoacetic resistant Herpes simplex virus. Phytomedicine, 4(4), 347-352.
Mizui, T., Yamashina, S., Tanida, I., Takei, Y., Ueno, T., Sakamoto, N., Ikejima, K., Kitamura, T., Enomoto, N., Sakai, T., Kominami, E., ＆ Watanabe, S. (2010). Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol, 45(2), 195-203.
Moore, P. A., Rosen, C. A., ＆ Carter, K. C. (1996). Assignment of the human FKBP12-rapamycin-associated protein (FRAP) gene to chromosome 1p36 by fluorescence in situ hybridization. Genomics, 33(2), 331-332.
Morrison, J., Laurent-Rolle, M., Maestre, A. M., Rajsbaum, R., Pisanelli, G., Simon, V., Mulder, L. C., Fernandez-Sesma, A., ＆ Garcia-Sastre, A. (2013). Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS Pathog, 9(3), e1003265.
Morrison, T. E., ＆ Diamond, M. S. (2017). Animal Models of Zika Virus Infection, Pathogenesis, and Immunity. J Virol, 91(8).
Muller, D. A., ＆ Young, P. R. (2013). The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker. Antiviral Res, 98(2), 192-208.
Munoz-Jordan, J. L., Laurent-Rolle, M., Ashour, J., Martinez-Sobrido, L., Ashok, M., Lipkin, W. I., ＆ Garcia-Sastre, A. (2005). Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol, 79(13), 8004-8013.
Musso, D., Cao-Lormeau, V. M., ＆ Gubler, D. J. (2015). Zika virus: following the path of dengue and chikungunya? Lancet, 386(9990), 243-244.
Musso, D., ＆ Gubler, D. J. (2016). Zika Virus. Clin Microbiol Rev, 29(3), 487-524.
Nasirudeen, A. M., Wong, H. H., Thien, P., Xu, S., Lam, K. P., ＆ Liu, D. X. (2011). RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis, 5(1), e926.
Naveh, E., Werman, M. J., Sabo, E., ＆ Neeman, I. (2002). Defatted avocado pulp reduces body weight and total hepatic fat but increases plasma cholesterol in male rats fed diets with cholesterol. J Nutr, 132(7), 2015-2018.
Neeman, I., Lifshitz, A., ＆ Kashman, Y. (1970). New antibacterial agent isolated from the avocado pear. Appl Microbiol, 19(3), 470-473.
Ngo, M., ＆ Ridgway, N. D. (2009). Oxysterol binding protein-related Protein 9 (ORP9) is a cholesterol transfer protein that regulates Golgi structure and function. Mol Biol Cell, 20(5), 1388-1399.
Nguyen, N. M., Tran, C. N., Phung, L. K., Duong, K. T., Huynh Hle, A., Farrar, J., Nguyen, Q. T., Tran, H. T., Nguyen, C. V., Merson, L., Hoang, L. T., Hibberd, M. L., Aw, P. P., Wilm, A., Nagarajan, N., Nguyen, D. T., Pham, M. P., Nguyen, T. T., Javanbakht, H., Klumpp, K., Hammond, J., Petric, R., Wolbers, M., Nguyen, C. T., ＆ Simmons, C. P. (2013). A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis, 207(9), 1442-1450.
Oh, Y., Zhang, F., Wang, Y., Lee, E. M., Choi, I. Y., Lim, H., Mirakhori, F., Li, R., Huang, L., Xu, T., Wu, H., Li, C., Qin, C. F., Wen, Z., Wu, Q. F., Tang, H., Xu, Z., Jin, P., Song, H., Ming, G. L., ＆ Lee, G. (2017). Zika virus directly infects peripheral neurons and induces cell death. Nat Neurosci, 20(9), 1209-1212.
Panossian, A., ＆ Wikman, G. (2008). Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol, 118(2), 183-212.
Parisien, J. P., Lau, J. F., Rodriguez, J. J., Sullivan, B. M., Moscona, A., Parks, G. D., Lamb, R. A., ＆ Horvath, C. M. (2001). The V protein of human parainfluenza virus 2 antagonizes type I interferon responses by destabilizing signal transducer and activator of transcription 2. Virology, 283(2), 230-239.
Park, S. Y., Park, S. J., Park, T. G., Rajasekar, S., Lee, S. J., ＆ Choi, Y. W. (2013). Schizandrin C exerts anti-neuroinflammatory effects by upregulating phase II detoxifying/antioxidant enzymes in microglia. Int Immunopharmacol, 17(2), 415-426.
Pawitwar, S. S., Dhar, S., Tiwari, S., Ojha, C. R., Lapierre, J., Martins, K., Rodzinski, A., Parira, T., Paudel, I., Li, J., Dutta, R. K., Silva, M. R., Kaushik, A., ＆ El-Hage, N. (2017). Overview on the Current Status of Zika Virus Pathogenesis and Animal Related Research. J Neuroimmune Pharmacol, 12(3), 371-388.
Peng, H., Liu, B., Yves, T. D., He, Y., Wang, S., Tang, H., Ren, H., Zhao, P., Qi, Z., ＆ Qin, Z. (2018). Zika Virus Induces Autophagy in Human Umbilical Vein Endothelial Cells. Viruses, 10(5).
Petersen, L. R., Jamieson, D. J., Powers, A. M., ＆ Honein, M. A. (2016). Zika Virus. N Engl J Med, 374(16), 1552-1563.
Polacek, C., Foley, J. E., ＆ Harris, E. (2009). Conformational changes in the solution structure of the dengue virus 5' end in the presence and absence of the 3' untranslated region. J Virol, 83(2), 1161-1166.
Polonio, C. M., de Freitas, C. L., Zanluqui, N. G., ＆ Peron, J. P. S. (2017). Zika virus congenital syndrome: experimental models and clinical aspects. J Venom Anim Toxins Incl Trop Dis, 23, 41.
Prentice, E., Jerome, W. G., Yoshimori, T., Mizushima, N., ＆ Denison, M. R. (2004). Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem, 279(11), 10136-10141.
Reiss, S., Rebhan, I., Backes, P., Romero-Brey, I., Erfle, H., Matula, P., Kaderali, L., Poenisch, M., Blankenburg, H., Hiet, M. S., Longerich, T., Diehl, S., Ramirez, F., Balla, T., Rohr, K., Kaul, A., Buhler, S., Pepperkok, R., Lengauer, T., Albrecht, M., Eils, R., Schirmacher, P., Lohmann, V., ＆ Bartenschlager, R. (2011). Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell Host Microbe, 9(1), 32-45.
Retallack, H., Di Lullo, E., Arias, C., Knopp, K. A., Laurie, M. T., Sandoval-Espinosa, C., Mancia Leon, W. R., Krencik, R., Ullian, E. M., Spatazza, J., Pollen, A. A., Mandel-Brehm, C., Nowakowski, T. J., Kriegstein, A. R., ＆ DeRisi, J. L. (2016). Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A, 113(50), 14408-14413.
Rossi, S. L., Tesh, R. B., Azar, S. R., Muruato, A. E., Hanley, K. A., Auguste, A. J., Langsjoen, R. M., Paessler, S., Vasilakis, N., ＆ Weaver, S. C. (2016). Characterization of a Novel Murine Model to Study Zika Virus. Am J Trop Med Hyg, 94(6), 1362-1369.
Sarmiento-Ospina, A., Vasquez-Serna, H., Jimenez-Canizales, C. E., Villamil-Gomez, W. E., ＆ Rodriguez-Morales, A. J. (2016). Zika virus associated deaths in Colombia. Lancet Infect Dis, 16(5), 523-524.
Schaefer, A., Schneeberger, Y., Stenzig, J., Biermann, D., Jelinek, M., Reichenspurner, H., Eschenhagen, T., Ehmke, H., ＆ Schwoerer, A. P. (2016). A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation. PLoS One, 11(2), e0148259.
Shi, J., ＆ Luo, H. (2012). Interplay between the cellular autophagy machinery and positive-stranded RNA viruses. Acta Biochim Biophys Sin (Shanghai), 44(5), 375-384.
Simon-Loriere, E., Lin, R. J., Kalayanarooj, S. M., Chuansumrit, A., Casademont, I., Lin, S. Y., Yu, H. P., Lert-Itthiporn, W., Chaiyaratana, W., Tangthawornchaikul, N., Tangnararatchakit, K., Vasanawathana, S., Chang, B. L., Suriyaphol, P., Yoksan, S., Malasit, P., Despres, P., Paul, R., Lin, Y. L., ＆ Sakuntabhai, A. (2015). High Anti-Dengue Virus Activity of the OAS Gene Family Is Associated With Increased Severity of Dengue. J Infect Dis, 212(12), 2011-2020.
Sumathy, K., Kulkarni, B., Gondu, R. K., Ponnuru, S. K., Bonguram, N., Eligeti, R., Gadiyaram, S., Praturi, U., Chougule, B., Karunakaran, L., ＆ Ella, K. M. (2017). Protective efficacy of Zika vaccine in AG129 mouse model. Sci Rep, 7, 46375.
Szaba, F. M., Tighe, M., Kummer, L. W., Lanzer, K. G., Ward, J. M., Lanthier, P., Kim, I. J., Kuki, A., Blackman, M. A., Thomas, S. J., ＆ Lin, J. S. (2018). Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. PLoS Pathog, 14(4), e1006994.
Tian, J., Wang, Y., Guo, H., ＆ Li, R. (2015). The Akt/mTOR/p70S6K pathway is activated in IgA nephropathy and rapamycin may represent a viable treatment option. Exp Mol Pathol.
Trivedi, C. M., Luo, Y., Yin, Z., Zhang, M., Zhu, W., Wang, T., Floss, T., Goettlicher, M., Noppinger, P. R., Wurst, W., Ferrari, V. A., Abrams, C. S., Gruber, P. J., ＆ Epstein, J. A. (2007). Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med, 13(3), 324-331.
Tseng, C. K., Lin, C. K., Wu, Y. H., Chen, Y. H., Chen, W. C., Young, K. C., ＆ Lee, J. C. (2016). Human heme oxygenase 1 is a potential host cell factor against dengue virus replication. Sci Rep, 6, 32176.
Ubol, S., Masrinoul, P., Chaijaruwanich, J., Kalayanarooj, S., Charoensirisuthikul, T., ＆ Kasisith, J. (2008). Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of dengue fever but not dengue hemorrhagic fever. J Infect Dis, 197(10), 1459-1467.
Wang, H., Perry, J. W., Lauring, A. S., Neddermann, P., De Francesco, R., ＆ Tai, A. W. (2014). Oxysterol-binding protein is a phosphatidylinositol 4-kinase effector required for HCV replication membrane integrity and cholesterol trafficking. Gastroenterology, 146(5), 1373-1385 e1371-1311.
Wang, S., Hong, S., Deng, Y. Q., Ye, Q., Zhao, L. Z., Zhang, F. C., Qin, C. F., ＆ Xu, Z. (2017). Transfer of convalescent serum to pregnant mice prevents Zika virus infection and microcephaly in offspring. Cell Res, 27(1), 158-160.
Willison, H. J. (2005). The immunobiology of Guillain-Barre syndromes. J Peripher Nerv Syst, 10(2), 94-112.
Wu, Y. H., Tseng, C. K., Lin, C. K., Wei, C. K., Lee, J. C., ＆ Young, K. C. (2018). ICR suckling mouse model of Zika virus infection for disease modeling and drug validation. PLoS Negl Trop Dis, 12(10), e0006848.
Wu, Y. H., Tseng, C. K., Wu, H. C., Wei, C. K., Lin, C. K., Chen, I. S., Chang, H. S., ＆ Lee, J. C. (2019). Avocado (Persea americana) fruit extract (2R,4R)-1,2,4-trihydroxyheptadec-16-yne inhibits dengue virus replication via upregulation of NF-kappaB-dependent induction of antiviral interferon responses. Sci Rep, 9(1), 423.
Xu, L., Grandi, N., Del Vecchio, C., Mandas, D., Corona, A., Piano, D., Esposito, F., Parolin, C., ＆ Tramontano, E. (2015). From the traditional Chinese medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors. J Microbiol, 53(4), 288-293.
Yang, C. F., Gopula, B., Liang, J. J., Li, J. K., Chen, S. Y., Lee, Y. L., Chen, C. S., ＆ Lin, Y. L. (2018). Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de novo pyrimidine biosynthesis. Emerg Microbes Infect, 7(1), 187.
Yin, Z., Chen, Y. L., Schul, W., Wang, Q. Y., Gu, F., Duraiswamy, J., Kondreddi, R. R., Niyomrattanakit, P., Lakshminarayana, S. B., Goh, A., Xu, H. Y., Liu, W., Liu, B., Lim, J. Y., Ng, C. Y., Qing, M., Lim, C. C., Yip, A., Wang, G., Chan, W. L., Tan, H. P., Lin, K., Zhang, B., Zou, G., Bernard, K. A., Garrett, C., Beltz, K., Dong, M., Weaver, M., He, H., Pichota, A., Dartois, V., Keller, T. H., ＆ Shi, P. Y. (2009). An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci U S A, 106(48), 20435-20439.
Yu, C. Y., Chang, T. H., Liang, J. J., Chiang, R. L., Lee, Y. L., Liao, C. L., ＆ Lin, Y. L. (2012). Dengue virus targets the adaptor protein MITA to subvert host innate immunity. PLoS Pathog, 8(6), e1002780.
Yu, J., Liu, X., Ke, C., Wu, Q., Lu, W., Qin, Z., He, X., Liu, Y., Deng, J., Xu, S., Li, Y., Zhu, L., Wan, C., Zhang, Q., Xiao, W., Xie, Q., Zhang, B., ＆ Zhao, W. (2017). Effective Suckling C57BL/6, Kunming, and BALB/c Mouse Models with Remarkable Neurological Manifestation for Zika Virus Infection. Viruses, 9(7).
Yu, J. S., Wu, Y. H., Tseng, C. K., Lin, C. K., Hsu, Y. C., Chen, Y. H., ＆ Lee, J. C. (2017). Schisandrin A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway. Sci Rep, 7, 45171.
Yuan, G., Liu, Y., Li, T., Wang, Y., Sheng, Y., ＆ Guan, M. (2011). Simultaneous and rapid determination of main lignans in different parts of Schisandra sphenanthera by micellar electrokinetic capillary chromatography. Molecules, 16(5), 3713-3722.
Zhang, H. L., Ye, H. Q., Liu, S. Q., Deng, C. L., Li, X. D., Shi, P. Y., ＆ Zhang, B. (2017). West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5. J Virol, 91(18).
Zhang, L., Hong, Z., Lin, W., Shao, R. X., Goto, K., Hsu, V. W., ＆ Chung, R. T. (2012). ARF1 and GBF1 generate a PI4P-enriched environment supportive of hepatitis C virus replication. PLoS One, 7(2), e32135.
Zhou, Q. Y., Huang, J. N., Zhu, M. J., ＆ Zhao, S. H. (2009). Molecular characterization and association analysis with production traits of the porcine INPP5F gene. Mol Biol Rep, 36(5), 1095-1098.
Zhou, X., Yang, J., Zhang, Z., Zhang, L., Zhu, B., Lie, L., Huang, Y., Ma, R., Zhou, C., Hu, S., Wen, Q., ＆ Ma, L. (2019). Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages. Int J Mol Sci, 20(3).
Zhu, W., Trivedi, C. M., Zhou, D., Yuan, L., Lu, M. M., ＆ Epstein, J. A. (2009). Inpp5f is a polyphosphoinositide phosphatase that regulates cardiac hypertrophic responsiveness. Circ Res, 105(12), 1240-1247.
Zhu, X., He, Z., Hu, Y., Wen, W., Lin, C., Yu, J., Pan, J., Li, R., Deng, H., Liao, S., Yuan, J., Wu, J., Li, J., ＆ Li, M. (2014). MicroRNA-30e* suppresses dengue virus replication by promoting NF-kappaB-dependent IFN production. PLoS Negl Trop Dis, 8(8), e3088.
Zompi, S., ＆ Harris, E. (2012). Animal models of dengue virus infection. Viruses, 4(1), 62-82.