The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection
The dengue virus presents a serious threat to human health globally and can cause severe, even life-threatening, illness. Dengue virus (DENV) is endemic on all continents except Antarctica, and it is estimated that more than 100 million people are infected each year. Herein, we further mine the data...
Published in: | Frontiers in Microbiology |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Frontiers Media S.A.
2020
|
Subjects: | |
Online Access: | https://doi.org/10.3389/fmicb.2020.00024 https://doaj.org/article/ac1ab5cca49447bea6012ee537b4d771 |
id |
ftdoajarticles:oai:doaj.org/article:ac1ab5cca49447bea6012ee537b4d771 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:ac1ab5cca49447bea6012ee537b4d771 2023-05-15T13:55:34+02:00 The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection Ashleigh R. Murphy Schafer Jessica L. Smith Kara M. Pryke Victor R. DeFilippis Alec J. Hirsch 2020-02-01T00:00:00Z https://doi.org/10.3389/fmicb.2020.00024 https://doaj.org/article/ac1ab5cca49447bea6012ee537b4d771 EN eng Frontiers Media S.A. https://www.frontiersin.org/article/10.3389/fmicb.2020.00024/full https://doaj.org/toc/1664-302X 1664-302X doi:10.3389/fmicb.2020.00024 https://doaj.org/article/ac1ab5cca49447bea6012ee537b4d771 Frontiers in Microbiology, Vol 11 (2020) dengue flavivirus unfolded protein response microRNA ubiquitin Microbiology QR1-502 article 2020 ftdoajarticles https://doi.org/10.3389/fmicb.2020.00024 2022-12-31T09:35:16Z The dengue virus presents a serious threat to human health globally and can cause severe, even life-threatening, illness. Dengue virus (DENV) is endemic on all continents except Antarctica, and it is estimated that more than 100 million people are infected each year. Herein, we further mine the data from a previously described screen for microRNAs (miRNAs) that block flavivirus replication. We use miR-424, a member of the miR-15/16 family, as a tool to further dissect the role of host cell proteins during DENV infection. We observed that miR-424 suppresses expression of the E3 ubiquitin ligase SIAH1, which is normally induced during dengue virus 2 (DENV2) infection through activation of the unfolded protein response (UPR). Specific siRNA-mediated knockdown of SIAH1 also results in inhibition of DENV replication, demonstrating that this target is at least partly responsible for the antiviral activity of miR-424. We further show that SIAH1 binds to and ubiquitinates the innate immune adaptor protein MyD88 and that the antiviral effect of SIAH1 knockdown is reduced in cells in which MyD88 has been deleted by CRISPR/Cas9 gene editing. Additionally, MyD88-dependent signaling, triggered either by DENV2 infection or the Toll-like receptor 7 (TLR7) ligand imiquimod, is increased in cells in which SIAH1 has been knocked down by miR-424 or a SIAH1-specific siRNA. These observations suggest an additional pathway by which DENV2 harnesses aspects of the UPR to dampen the host innate immune response and promote viral replication. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles Frontiers in Microbiology 11 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
dengue flavivirus unfolded protein response microRNA ubiquitin Microbiology QR1-502 |
spellingShingle |
dengue flavivirus unfolded protein response microRNA ubiquitin Microbiology QR1-502 Ashleigh R. Murphy Schafer Jessica L. Smith Kara M. Pryke Victor R. DeFilippis Alec J. Hirsch The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
topic_facet |
dengue flavivirus unfolded protein response microRNA ubiquitin Microbiology QR1-502 |
description |
The dengue virus presents a serious threat to human health globally and can cause severe, even life-threatening, illness. Dengue virus (DENV) is endemic on all continents except Antarctica, and it is estimated that more than 100 million people are infected each year. Herein, we further mine the data from a previously described screen for microRNAs (miRNAs) that block flavivirus replication. We use miR-424, a member of the miR-15/16 family, as a tool to further dissect the role of host cell proteins during DENV infection. We observed that miR-424 suppresses expression of the E3 ubiquitin ligase SIAH1, which is normally induced during dengue virus 2 (DENV2) infection through activation of the unfolded protein response (UPR). Specific siRNA-mediated knockdown of SIAH1 also results in inhibition of DENV replication, demonstrating that this target is at least partly responsible for the antiviral activity of miR-424. We further show that SIAH1 binds to and ubiquitinates the innate immune adaptor protein MyD88 and that the antiviral effect of SIAH1 knockdown is reduced in cells in which MyD88 has been deleted by CRISPR/Cas9 gene editing. Additionally, MyD88-dependent signaling, triggered either by DENV2 infection or the Toll-like receptor 7 (TLR7) ligand imiquimod, is increased in cells in which SIAH1 has been knocked down by miR-424 or a SIAH1-specific siRNA. These observations suggest an additional pathway by which DENV2 harnesses aspects of the UPR to dampen the host innate immune response and promote viral replication. |
format |
Article in Journal/Newspaper |
author |
Ashleigh R. Murphy Schafer Jessica L. Smith Kara M. Pryke Victor R. DeFilippis Alec J. Hirsch |
author_facet |
Ashleigh R. Murphy Schafer Jessica L. Smith Kara M. Pryke Victor R. DeFilippis Alec J. Hirsch |
author_sort |
Ashleigh R. Murphy Schafer |
title |
The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
title_short |
The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
title_full |
The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
title_fullStr |
The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
title_full_unstemmed |
The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection |
title_sort |
e3 ubiquitin ligase siah1 targets myd88 for proteasomal degradation during dengue virus infection |
publisher |
Frontiers Media S.A. |
publishDate |
2020 |
url |
https://doi.org/10.3389/fmicb.2020.00024 https://doaj.org/article/ac1ab5cca49447bea6012ee537b4d771 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Frontiers in Microbiology, Vol 11 (2020) |
op_relation |
https://www.frontiersin.org/article/10.3389/fmicb.2020.00024/full https://doaj.org/toc/1664-302X 1664-302X doi:10.3389/fmicb.2020.00024 https://doaj.org/article/ac1ab5cca49447bea6012ee537b4d771 |
op_doi |
https://doi.org/10.3389/fmicb.2020.00024 |
container_title |
Frontiers in Microbiology |
container_volume |
11 |
_version_ |
1766262273060372480 |