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Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response

In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact...

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Autores principales: Li, Yi-Lin, Gong, Xiu-Ying, Qu, Zi-Ling, Zhao, Xiang, Dan, Cheng, Sun, Hao-Yu, An, Li-Li, Gui, Jian-Fang, Zhang, Yi-Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003058/
https://www.ncbi.nlm.nih.gov/pubmed/36902023
http://dx.doi.org/10.3390/ijms24054592
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author Li, Yi-Lin
Gong, Xiu-Ying
Qu, Zi-Ling
Zhao, Xiang
Dan, Cheng
Sun, Hao-Yu
An, Li-Li
Gui, Jian-Fang
Zhang, Yi-Bing
author_facet Li, Yi-Lin
Gong, Xiu-Ying
Qu, Zi-Ling
Zhao, Xiang
Dan, Cheng
Sun, Hao-Yu
An, Li-Li
Gui, Jian-Fang
Zhang, Yi-Bing
author_sort Li, Yi-Lin
collection PubMed
description In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a–d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response.
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spelling pubmed-100030582023-03-11 Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response Li, Yi-Lin Gong, Xiu-Ying Qu, Zi-Ling Zhao, Xiang Dan, Cheng Sun, Hao-Yu An, Li-Li Gui, Jian-Fang Zhang, Yi-Bing Int J Mol Sci Article In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a–d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response. MDPI 2023-02-27 /pmc/articles/PMC10003058/ /pubmed/36902023 http://dx.doi.org/10.3390/ijms24054592 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yi-Lin
Gong, Xiu-Ying
Qu, Zi-Ling
Zhao, Xiang
Dan, Cheng
Sun, Hao-Yu
An, Li-Li
Gui, Jian-Fang
Zhang, Yi-Bing
Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title_full Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title_fullStr Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title_full_unstemmed Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title_short Zebrafish HERC7c Acts as an Inhibitor of Fish IFN Response
title_sort zebrafish herc7c acts as an inhibitor of fish ifn response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003058/
https://www.ncbi.nlm.nih.gov/pubmed/36902023
http://dx.doi.org/10.3390/ijms24054592
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