C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3.
The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factor...
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ftdoajarticles:oai:doaj.org/article:596307fe680044f780b8df41effaa312 2023-05-15T15:09:23+02:00 C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. Yun Wu Xinyu Yang Zhicheng Yao Xinhuai Dong Danrui Zhang Yiwen Hu Shihao Zhang Jiajie Lin Jiahui Chen Shu An Hengming Ye Shuqing Zhang Ziying Qiu Zhenjian He Mingxing Huang Guohong Wei Xun Zhu 2020-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008083 https://doaj.org/article/596307fe680044f780b8df41effaa312 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008083 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008083 https://doaj.org/article/596307fe680044f780b8df41effaa312 PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008083 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008083 2022-12-31T15:20:16Z The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action. In this work, we focused our investigation on the possible antiviral effect of a novel ISG, C19orf66 in response to ZIKV infection and the associated mechanisms. We found that ZIKV infection could induce C19orf66 expression in ZIKV-permissive cells, and such an overexpression of C19orf66 remarkably suppressed ZIKV replication. Conversely, the depletion of C19orf66 led to a significant increase in viral replication. Furthermore, C19orf66 was found to interact and co-localize with ZIKV nonstructural protein 3 (NS3), thus inducing NS3 degradation via a lysosome-dependent pathway. Taken together, this study identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically degrading a viral nonstructural protein. These findings uncovered an intriguing mechanism of C19orf66 that targeting NS3 protein of ZIKV, providing clues for understanding the actions of innate immunity, and affording the possible availability of new drug targets that can be used for therapeutic intervention. Article in Journal/Newspaper Arctic Human health Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 3 e0008083 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yun Wu Xinyu Yang Zhicheng Yao Xinhuai Dong Danrui Zhang Yiwen Hu Shihao Zhang Jiajie Lin Jiahui Chen Shu An Hengming Ye Shuqing Zhang Ziying Qiu Zhenjian He Mingxing Huang Guohong Wei Xun Zhu C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action. In this work, we focused our investigation on the possible antiviral effect of a novel ISG, C19orf66 in response to ZIKV infection and the associated mechanisms. We found that ZIKV infection could induce C19orf66 expression in ZIKV-permissive cells, and such an overexpression of C19orf66 remarkably suppressed ZIKV replication. Conversely, the depletion of C19orf66 led to a significant increase in viral replication. Furthermore, C19orf66 was found to interact and co-localize with ZIKV nonstructural protein 3 (NS3), thus inducing NS3 degradation via a lysosome-dependent pathway. Taken together, this study identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically degrading a viral nonstructural protein. These findings uncovered an intriguing mechanism of C19orf66 that targeting NS3 protein of ZIKV, providing clues for understanding the actions of innate immunity, and affording the possible availability of new drug targets that can be used for therapeutic intervention. |
format |
Article in Journal/Newspaper |
author |
Yun Wu Xinyu Yang Zhicheng Yao Xinhuai Dong Danrui Zhang Yiwen Hu Shihao Zhang Jiajie Lin Jiahui Chen Shu An Hengming Ye Shuqing Zhang Ziying Qiu Zhenjian He Mingxing Huang Guohong Wei Xun Zhu |
author_facet |
Yun Wu Xinyu Yang Zhicheng Yao Xinhuai Dong Danrui Zhang Yiwen Hu Shihao Zhang Jiajie Lin Jiahui Chen Shu An Hengming Ye Shuqing Zhang Ziying Qiu Zhenjian He Mingxing Huang Guohong Wei Xun Zhu |
author_sort |
Yun Wu |
title |
C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
title_short |
C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
title_full |
C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
title_fullStr |
C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
title_full_unstemmed |
C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. |
title_sort |
c19orf66 interrupts zika virus replication by inducing lysosomal degradation of viral ns3. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008083 https://doaj.org/article/596307fe680044f780b8df41effaa312 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Human health |
genre_facet |
Arctic Human health |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008083 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008083 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008083 https://doaj.org/article/596307fe680044f780b8df41effaa312 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008083 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
3 |
container_start_page |
e0008083 |
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1766340592707567616 |