title: Modulation of the immune-related gene responses to protect mice against Japanese encephalitis virus using the antimicrobial peptide, tilapia hepcidin 1-5.
abstract: Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. After infection, it is commonly associated with inflammatory reactions and neurological disease. There is still no effective antiviral drug available against Japanese encephalitis virus infection. Recently, a number of investigators found that antimicrobial peptide (AMPs) present a broad range of biological activities including antimicrobial and immunomodulatory activities. In this study, we found that an AMP, tilapia hepcidin (TH)1-5, caused no harm to either cells or test animals during the test course and could control JEV viral infection in BHK-21 cells. Mice co-injected with TH1-5/JEV and subsequently subjected to JEV re-challenge survived and behaved normally. The neuroprotective effects were associated with marked decreases in: (i) the viral load and viral replication within the brain, (ii) neuronal death, and (iii) secondary inflammation resulting from microglial activation. TH1-5 was also determined to enhance adaptive immunity by elevating levels of anti-JEV-neutralizing antibodies in the serum. The microarray data also showed that TH1-5 modulated Socs-6, interleukin (IL)-6, Toll-like receptor (TLR)-1, TLR-7, caspase-4, interferon (IFN)-β1, ATF-3, and several immune-responsive genes to protect mice against JEV infection. In addition, TH1-5 was confirmed to modulate the expressions of several proinflammatory and immune-responsive genes, such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α, IFN-γ and monocyte chemoattractant protein (MCP)-1 at both the transcriptional and translational levels in JEV-infected mice. In conclusion, our findings provide mechanistic insights into the actions of TH1-5 against JEV. Results from our in vivo and in vitro experiments clearly indicate that TH1-5 has antiviral, neuroprotective, anti-inflammatory, and immunomodulatory activities. Furthermore, TH1-5 successfully reduced the severity of disease induced by JEV. Our results point out that TH1-5 is a promising candidate for further development as an antiviral agent against JEV infection.
authors: Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan.
authors: Han-Ning
authors: HN
authors: Huang
authors: Venugopal
authors: V
authors: Rajanbabu
authors: Chieh-Yu
authors: CY
authors: Pan
authors: Yi-Lin
authors: YL
authors: Chan
authors: Cho-Fat
authors: CF
authors: Hui
authors: Jyh-Yih
authors: JY
authors: Chen
authors: Chang-Jer
authors: CJ
authors: Wu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000187:drug effects* / Q000276:immunology; D004672:Encephalitis, Japanese / Q000188:drug therapy / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D064451:Hepcidins; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma