The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function.
Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Her...
Published in: | PLOS Neglected Tropical Diseases |
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Online Access: | https://doi.org/10.1371/journal.pntd.0007537 https://doaj.org/article/4470d0a87ce84ea5b4f2b8200d3320c5 |
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ftdoajarticles:oai:doaj.org/article:4470d0a87ce84ea5b4f2b8200d3320c5 2023-05-15T15:10:24+02:00 The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. Darong Yang Nan L Li Dahai Wei Baoming Liu Fang Guo Husni Elbahesh Yunzhi Zhang Zhi Zhou Guo-Yun Chen Kui Li 2019-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007537 https://doaj.org/article/4470d0a87ce84ea5b4f2b8200d3320c5 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007537 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007537 https://doaj.org/article/4470d0a87ce84ea5b4f2b8200d3320c5 PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007537 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007537 2022-12-31T05:55:01Z Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 6 e0007537 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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 Darong Yang Nan L Li Dahai Wei Baoming Liu Fang Guo Husni Elbahesh Yunzhi Zhang Zhi Zhou Guo-Yun Chen Kui Li The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections. |
format |
Article in Journal/Newspaper |
author |
Darong Yang Nan L Li Dahai Wei Baoming Liu Fang Guo Husni Elbahesh Yunzhi Zhang Zhi Zhou Guo-Yun Chen Kui Li |
author_facet |
Darong Yang Nan L Li Dahai Wei Baoming Liu Fang Guo Husni Elbahesh Yunzhi Zhang Zhi Zhou Guo-Yun Chen Kui Li |
author_sort |
Darong Yang |
title |
The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
title_short |
The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
title_full |
The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
title_fullStr |
The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
title_full_unstemmed |
The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. |
title_sort |
e3 ligase trim56 is a host restriction factor of zika virus and depends on its rna-binding activity but not mirna regulation, for antiviral function. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007537 https://doaj.org/article/4470d0a87ce84ea5b4f2b8200d3320c5 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007537 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007537 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007537 https://doaj.org/article/4470d0a87ce84ea5b4f2b8200d3320c5 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007537 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
6 |
container_start_page |
e0007537 |
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1766341441287618560 |