Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells.
Interferons (IFNs) are critical cytokines that regulate immune response against virus infections. Dengue virus (DV) infections are a major public health concern worldwide, and especially in Asia. In the present study, we investigated the effects and mechanisms of action of IFN-induced protein with t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3817122?pdf=render |
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| author | Yu-Lin Hsu Shao-Fu Shi Wan-Lin Wu Ling-Jun Ho Jenn-Haung Lai |
| author_facet | Yu-Lin Hsu Shao-Fu Shi Wan-Lin Wu Ling-Jun Ho Jenn-Haung Lai |
| author_sort | Yu-Lin Hsu |
| collection | DOAJ |
| description | Interferons (IFNs) are critical cytokines that regulate immune response against virus infections. Dengue virus (DV) infections are a major public health concern worldwide, and especially in Asia. In the present study, we investigated the effects and mechanisms of action of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in human lung epithelial cells. The results demonstrated that DV infection induced expression of several IFITs, including IFIT1, IFIT2, IFIT3, and IFIT5 in A549 cells. Induction of IFIT3 by DV infection was also observed in human dendritic cells. In a knockdown study, we showed that a signal transducer and activator of transcription 2 (STAT2), but not STAT1 or STAT3, regulated DV-induced IFIT3 production. By using several different methods to evaluate cell death, we demonstrated that knockdown of IFIT3 led to cellular apoptosis. Furthermore, knockdown of IFIT3 induced the expression of several apoptotic regulators such as caspase 3, caspase 8, caspase 9, and Bcl-2-associated X protein (BAX). Such apoptotic effects and mechanisms were synergistically enhanced after DV infection. Moreover, under conditions of IFIT3 deficiency, viral production increased, suggesting an anti-viral effect of IFIT3. Interestingly, DV could suppress IFN-α-induced but not IFN-γ-induced IFIT3 expression, a phenomenon similar to the regulation of STATs by DV. In conclusion, this study revealed some mechanisms of IFIT3 induction, and also demonstrated the protective roles of IFIT3 following IFN-α production in DV infection of human lung epithelial cells. |
| first_indexed | 2024-12-21T19:46:27Z |
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| id | doaj.art-8c455ce61eaa4e4d8adebefe03bb88b2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T19:46:27Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-8c455ce61eaa4e4d8adebefe03bb88b22022-12-21T18:52:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e7951810.1371/journal.pone.0079518Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells.Yu-Lin HsuShao-Fu ShiWan-Lin WuLing-Jun HoJenn-Haung LaiInterferons (IFNs) are critical cytokines that regulate immune response against virus infections. Dengue virus (DV) infections are a major public health concern worldwide, and especially in Asia. In the present study, we investigated the effects and mechanisms of action of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in human lung epithelial cells. The results demonstrated that DV infection induced expression of several IFITs, including IFIT1, IFIT2, IFIT3, and IFIT5 in A549 cells. Induction of IFIT3 by DV infection was also observed in human dendritic cells. In a knockdown study, we showed that a signal transducer and activator of transcription 2 (STAT2), but not STAT1 or STAT3, regulated DV-induced IFIT3 production. By using several different methods to evaluate cell death, we demonstrated that knockdown of IFIT3 led to cellular apoptosis. Furthermore, knockdown of IFIT3 induced the expression of several apoptotic regulators such as caspase 3, caspase 8, caspase 9, and Bcl-2-associated X protein (BAX). Such apoptotic effects and mechanisms were synergistically enhanced after DV infection. Moreover, under conditions of IFIT3 deficiency, viral production increased, suggesting an anti-viral effect of IFIT3. Interestingly, DV could suppress IFN-α-induced but not IFN-γ-induced IFIT3 expression, a phenomenon similar to the regulation of STATs by DV. In conclusion, this study revealed some mechanisms of IFIT3 induction, and also demonstrated the protective roles of IFIT3 following IFN-α production in DV infection of human lung epithelial cells.http://europepmc.org/articles/PMC3817122?pdf=render |
| spellingShingle | Yu-Lin Hsu Shao-Fu Shi Wan-Lin Wu Ling-Jun Ho Jenn-Haung Lai Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. PLoS ONE |
| title | Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. |
| title_full | Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. |
| title_fullStr | Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. |
| title_full_unstemmed | Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. |
| title_short | Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. |
| title_sort | protective roles of interferon induced protein with tetratricopeptide repeats 3 ifit3 in dengue virus infection of human lung epithelial cells |
| url | http://europepmc.org/articles/PMC3817122?pdf=render |
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