Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway
Dengue virus (DENV) is the causative pathogen in the life-threatening dengue hemorrhagic fever and dengue shock syndrome. DENV is transmitted to humans via the bite of an infected <i>Aedes</i> mosquito. Approximately 100 million people are infected annually worldwide, and most of those l...
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doaj-cd637f61637b48f8bbe0f466b3fc54172021-04-11T23:01:53ZengMDPI AGViruses1999-49152021-04-011365965910.3390/v13040659Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon PathwayAtthapan Morchang0Shilu Malakar1Kanchanaphan Poonudom2Sansanee Noisakran3Pa-thai Yenchitsomanus4Thawornchai Limjindaporn5Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandMolecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, ThailandDivision of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDengue virus (DENV) is the causative pathogen in the life-threatening dengue hemorrhagic fever and dengue shock syndrome. DENV is transmitted to humans via the bite of an infected <i>Aedes</i> mosquito. Approximately 100 million people are infected annually worldwide, and most of those live in tropical and subtropical areas. There is still no effective drug or vaccine for treatment of DENV infection. In this study, we set forth to investigate the effect of melatonin, which is a natural hormone with multiple pharmacological functions, against DENV infection. Treatment with subtoxic doses of melatonin dose-dependently inhibited DENV production. Cross-protection across serotypes and various cell types was also observed. Time-of-addition assay suggested that melatonin exerts its influence during the post-entry step of viral infection. The antiviral activity of melatonin partly originates from activation of the sirtuin pathway since co-treatment with melatonin and the sirtuin 1 (SIRT1) inhibitor reversed the effect of melatonin treatment alone. Moreover, melatonin could modulate the transcription of antiviral genes that aid in suppression of DENV production. This antiviral mechanism of melatonin suggests a possible new strategy for treating DENV infection.https://www.mdpi.com/1999-4915/13/4/659melatonindengue virus infectionDENVsirtuin 1 (SIRT1)-mediated interferon (IFN) pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Atthapan Morchang Shilu Malakar Kanchanaphan Poonudom Sansanee Noisakran Pa-thai Yenchitsomanus Thawornchai Limjindaporn |
spellingShingle |
Atthapan Morchang Shilu Malakar Kanchanaphan Poonudom Sansanee Noisakran Pa-thai Yenchitsomanus Thawornchai Limjindaporn Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway Viruses melatonin dengue virus infection DENV sirtuin 1 (SIRT1)-mediated interferon (IFN) pathway |
author_facet |
Atthapan Morchang Shilu Malakar Kanchanaphan Poonudom Sansanee Noisakran Pa-thai Yenchitsomanus Thawornchai Limjindaporn |
author_sort |
Atthapan Morchang |
title |
Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway |
title_short |
Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway |
title_full |
Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway |
title_fullStr |
Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway |
title_full_unstemmed |
Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway |
title_sort |
melatonin inhibits dengue virus infection via the sirtuin 1-mediated interferon pathway |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2021-04-01 |
description |
Dengue virus (DENV) is the causative pathogen in the life-threatening dengue hemorrhagic fever and dengue shock syndrome. DENV is transmitted to humans via the bite of an infected <i>Aedes</i> mosquito. Approximately 100 million people are infected annually worldwide, and most of those live in tropical and subtropical areas. There is still no effective drug or vaccine for treatment of DENV infection. In this study, we set forth to investigate the effect of melatonin, which is a natural hormone with multiple pharmacological functions, against DENV infection. Treatment with subtoxic doses of melatonin dose-dependently inhibited DENV production. Cross-protection across serotypes and various cell types was also observed. Time-of-addition assay suggested that melatonin exerts its influence during the post-entry step of viral infection. The antiviral activity of melatonin partly originates from activation of the sirtuin pathway since co-treatment with melatonin and the sirtuin 1 (SIRT1) inhibitor reversed the effect of melatonin treatment alone. Moreover, melatonin could modulate the transcription of antiviral genes that aid in suppression of DENV production. This antiviral mechanism of melatonin suggests a possible new strategy for treating DENV infection. |
topic |
melatonin dengue virus infection DENV sirtuin 1 (SIRT1)-mediated interferon (IFN) pathway |
url |
https://www.mdpi.com/1999-4915/13/4/659 |
work_keys_str_mv |
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