Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity
Cyclooxygenase-2 (COX-2), one of the mediators of inflammation in response to viral infection, plays an important role in host antiviral defense system. But its role in Newcastle disease virus (NDV) proliferation process remains unclear. This study revealed that inhibition of COX-2 could benefit NDV...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00987/full |
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| author | Chongyang Wang Ting Wang Ruochen Hu Jiangkun Dai Haijin Liu Na Li Uwe Schneider Zengqi Yang Junru Wang |
| author_facet | Chongyang Wang Ting Wang Ruochen Hu Jiangkun Dai Haijin Liu Na Li Uwe Schneider Zengqi Yang Junru Wang |
| author_sort | Chongyang Wang |
| collection | DOAJ |
| description | Cyclooxygenase-2 (COX-2), one of the mediators of inflammation in response to viral infection, plays an important role in host antiviral defense system. But its role in Newcastle disease virus (NDV) proliferation process remains unclear. This study revealed that inhibition of COX-2 could benefit NDV proliferation and overexpression of COX-2 dose-dependently suppressed NDV proliferation. Overexpression of COX-2 also showed inhibitory effect on NDV-induced endoplasmic reticulum (ER)-stress and autophagy, also promoted the expression of antiviral genes. However, prostaglandin E2 (PGE2), the major product of COX-2, had indistinctive effects on NDV proliferation. At variant time point post viral infection, a tight regulation pattern of COX-2 by NDV was observed. Using inhibitors and siRNA against signaling molecules, the nuclear factor-κB (NF-κB) and melanoma differentiation-associated gene 5 (MDA5) were identified as critical factors for NDV induced COX-2 expression. Nonetheless, at late stage of NDV proliferation, substantial suppression of COX-2 protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Furthermore, three C ring-truncated canthin-6-one analogs were used to activate COX-2 expression and showed inhibitory effect on NDV proliferation with the effective concentrations on μM level. Taken together, these results illustrated a novel NDV-regulated cellular mechanism and indicated that COX-2 is an important regulator of NDV proliferation which can serve as a potential target for anti-NDV agents. |
| first_indexed | 2024-04-13T14:12:57Z |
| format | Article |
| id | doaj.art-439a8164ae734deabf3f676e0826cac3 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T14:12:57Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-439a8164ae734deabf3f676e0826cac32022-12-22T02:43:44ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-05-011110.3389/fmicb.2020.00987528154Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral ActivityChongyang Wang0Ting Wang1Ruochen Hu2Jiangkun Dai3Haijin Liu4Na Li5Uwe Schneider6Zengqi Yang7Junru Wang8College of Chemistry and Pharmacy, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Chemistry and Pharmacy, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Food Science and Technology, Northwest University, Xi’an, ChinaSchool of Chemistry, The University of Edinburgh, Edinburgh, United KingdomCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Chemistry and Pharmacy, Northwest A&F University, Yangling, ChinaCyclooxygenase-2 (COX-2), one of the mediators of inflammation in response to viral infection, plays an important role in host antiviral defense system. But its role in Newcastle disease virus (NDV) proliferation process remains unclear. This study revealed that inhibition of COX-2 could benefit NDV proliferation and overexpression of COX-2 dose-dependently suppressed NDV proliferation. Overexpression of COX-2 also showed inhibitory effect on NDV-induced endoplasmic reticulum (ER)-stress and autophagy, also promoted the expression of antiviral genes. However, prostaglandin E2 (PGE2), the major product of COX-2, had indistinctive effects on NDV proliferation. At variant time point post viral infection, a tight regulation pattern of COX-2 by NDV was observed. Using inhibitors and siRNA against signaling molecules, the nuclear factor-κB (NF-κB) and melanoma differentiation-associated gene 5 (MDA5) were identified as critical factors for NDV induced COX-2 expression. Nonetheless, at late stage of NDV proliferation, substantial suppression of COX-2 protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Furthermore, three C ring-truncated canthin-6-one analogs were used to activate COX-2 expression and showed inhibitory effect on NDV proliferation with the effective concentrations on μM level. Taken together, these results illustrated a novel NDV-regulated cellular mechanism and indicated that COX-2 is an important regulator of NDV proliferation which can serve as a potential target for anti-NDV agents.https://www.frontiersin.org/article/10.3389/fmicb.2020.00987/fullcyclooxygenase-2prostaglandin E2Newcastle disease viruscanthin-6-oneantiviral |
| spellingShingle | Chongyang Wang Ting Wang Ruochen Hu Jiangkun Dai Haijin Liu Na Li Uwe Schneider Zengqi Yang Junru Wang Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity Frontiers in Microbiology cyclooxygenase-2 prostaglandin E2 Newcastle disease virus canthin-6-one antiviral |
| title | Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity |
| title_full | Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity |
| title_fullStr | Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity |
| title_full_unstemmed | Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity |
| title_short | Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity |
| title_sort | cyclooxygenase 2 facilitates newcastle disease virus proliferation and is as a target for canthin 6 one antiviral activity |
| topic | cyclooxygenase-2 prostaglandin E2 Newcastle disease virus canthin-6-one antiviral |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.00987/full |
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