RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection.
Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understan...
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ftdoajarticles:oai:doaj.org/article:7889acaadf3c4bf9b2f4432587cbce2c 2023-05-15T15:11:05+02:00 RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. A M A Nasirudeen Hui Hui Wong Peiling Thien Shengli Xu Kong-Peng Lam Ding Xiang Liu 2011-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000926 https://doaj.org/article/7889acaadf3c4bf9b2f4432587cbce2c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3014945?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000926 https://doaj.org/article/7889acaadf3c4bf9b2f4432587cbce2c PLoS Neglected Tropical Diseases, Vol 5, Iss 1, p e926 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000926 2022-12-31T13:43:33Z Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll-like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 1 e926 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 A M A Nasirudeen Hui Hui Wong Peiling Thien Shengli Xu Kong-Peng Lam Ding Xiang Liu RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll-like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus. |
format |
Article in Journal/Newspaper |
author |
A M A Nasirudeen Hui Hui Wong Peiling Thien Shengli Xu Kong-Peng Lam Ding Xiang Liu |
author_facet |
A M A Nasirudeen Hui Hui Wong Peiling Thien Shengli Xu Kong-Peng Lam Ding Xiang Liu |
author_sort |
A M A Nasirudeen |
title |
RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
title_short |
RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
title_full |
RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
title_fullStr |
RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
title_full_unstemmed |
RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. |
title_sort |
rig-i, mda5 and tlr3 synergistically play an important role in restriction of dengue virus infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0000926 https://doaj.org/article/7889acaadf3c4bf9b2f4432587cbce2c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 1, p e926 (2011) |
op_relation |
http://europepmc.org/articles/PMC3014945?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000926 https://doaj.org/article/7889acaadf3c4bf9b2f4432587cbce2c |
op_doi |
https://doi.org/10.1371/journal.pntd.0000926 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
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1 |
container_start_page |
e926 |
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1766341999805333504 |