Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication.
Zika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which...
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ftdoajarticles:oai:doaj.org/article:a6351f353c20453b9b76777844b180be 2023-05-15T15:15:25+02:00 Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. Yufeng Yu Chengfeng Gao Chunxia Wen Peng Zou Xian Qi Carol J Cardona Zheng Xing 2022-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010366 https://doaj.org/article/a6351f353c20453b9b76777844b180be EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010366 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010366 https://doaj.org/article/a6351f353c20453b9b76777844b180be PLoS Neglected Tropical Diseases, Vol 16, Iss 5, p e0010366 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010366 2022-12-30T21:49:03Z Zika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which encodes 7 non-structural (NS) proteins, participating in viral replication and dysregulation of host immunity. Like those in many other viruses, NS proteins are considered to be products evolutionarily beneficiary to viruses and some are virulence factors. However, we found that some NS proteins encoded by ZIKV genome appeared to function against the viral replication. In this report we showed that exogenously expressed ZIKV NS2A and NS4A inhibited ZIKV infection by inhibiting viral RNA replication in microglial cells and astrocytes. To understand how viral NS proteins suppressed viral replication, we analyzed the transcriptome of the microglial cells and astrocytes and found that expression of NS4A induced the upregulation of ISGs, including MX1/2, OAS1/2/3, IFITM1, IFIT1, IFI6, IFI27, ISG15 or BST2 through activating the ISGF3 signaling pathway. Upregulation of these ISGs seemed to be related to the inhibition of ZIKV replication, since the anti-ZIKV function of NS4A was partially attenuated when the cells were treated with Abrocitinib, an inhibitor of the ISGF3 signaling pathway, or were knocked down with STAT2. Aborting the protein expression of NS4A, but not its nucleic acid, eliminated the antiviral activity of NS4A effectively. Dynamic expression of viral NS proteins was examined in ZIKV-infected microglial cells and astrocytes, which showed comparatively NS4A occurred later than other NS proteins during the infection. We hypothesize that NS4A may possess intrinsic features to serve as a unique type of pathogen associated molecular pattern (PAMP), detectable by the cells to induce an innate immune response, or function with other mechanisms, to restrict the viral replication to a certain level as a negative ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 5 e0010366 |
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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 Yufeng Yu Chengfeng Gao Chunxia Wen Peng Zou Xian Qi Carol J Cardona Zheng Xing Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Zika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which encodes 7 non-structural (NS) proteins, participating in viral replication and dysregulation of host immunity. Like those in many other viruses, NS proteins are considered to be products evolutionarily beneficiary to viruses and some are virulence factors. However, we found that some NS proteins encoded by ZIKV genome appeared to function against the viral replication. In this report we showed that exogenously expressed ZIKV NS2A and NS4A inhibited ZIKV infection by inhibiting viral RNA replication in microglial cells and astrocytes. To understand how viral NS proteins suppressed viral replication, we analyzed the transcriptome of the microglial cells and astrocytes and found that expression of NS4A induced the upregulation of ISGs, including MX1/2, OAS1/2/3, IFITM1, IFIT1, IFI6, IFI27, ISG15 or BST2 through activating the ISGF3 signaling pathway. Upregulation of these ISGs seemed to be related to the inhibition of ZIKV replication, since the anti-ZIKV function of NS4A was partially attenuated when the cells were treated with Abrocitinib, an inhibitor of the ISGF3 signaling pathway, or were knocked down with STAT2. Aborting the protein expression of NS4A, but not its nucleic acid, eliminated the antiviral activity of NS4A effectively. Dynamic expression of viral NS proteins was examined in ZIKV-infected microglial cells and astrocytes, which showed comparatively NS4A occurred later than other NS proteins during the infection. We hypothesize that NS4A may possess intrinsic features to serve as a unique type of pathogen associated molecular pattern (PAMP), detectable by the cells to induce an innate immune response, or function with other mechanisms, to restrict the viral replication to a certain level as a negative ... |
format |
Article in Journal/Newspaper |
author |
Yufeng Yu Chengfeng Gao Chunxia Wen Peng Zou Xian Qi Carol J Cardona Zheng Xing |
author_facet |
Yufeng Yu Chengfeng Gao Chunxia Wen Peng Zou Xian Qi Carol J Cardona Zheng Xing |
author_sort |
Yufeng Yu |
title |
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
title_short |
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
title_full |
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
title_fullStr |
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
title_full_unstemmed |
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication. |
title_sort |
intrinsic features of zika virus non-structural proteins ns2a and ns4a in the regulation of viral replication. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010366 https://doaj.org/article/a6351f353c20453b9b76777844b180be |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 5, p e0010366 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010366 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010366 https://doaj.org/article/a6351f353c20453b9b76777844b180be |
op_doi |
https://doi.org/10.1371/journal.pntd.0010366 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
16 |
container_issue |
5 |
container_start_page |
e0010366 |
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1766345775807201280 |