Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway

Newcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity a...

Full description

Bibliographic Details
Main Authors: Xiangwei Wang, Yanqing Jia, Juan Ren, Na Huo, Haijin Liu, Sa Xiao, Xinglong Wang, Zengqi Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcimb.2019.00317/full
id doaj-dd737179a8674cc7a44eaf30592c2967
record_format Article
spelling doaj-dd737179a8674cc7a44eaf30592c29672020-11-25T01:59:06ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-09-01910.3389/fcimb.2019.00317477985Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK PathwayXiangwei WangYanqing JiaJuan RenNa HuoHaijin LiuSa XiaoXinglong WangZengqi YangNewcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity are not well-understood. The suppressor of cytokine signaling 3 (SOCS3) inhibits the type I interferon-dependent antiviral signaling pathway by utilizing a feedback loop. In this study, we analyzed the transcriptome data of the chicken embryo and BF infected with NDV and found significant upregulation of SOCS3. Next, we demonstrated that NDV infection and nonstructural V protein induced the up-regulation of SOCS3. Furthermore, we showed that overexpression of SOCS3 facilitated viral replication and reduced the expression of phosphorylation STAT1, MX1, and OASL, while inhibition of SOCS3 with siRNAs reduced virus replication and promoted the expression of phosphorylation STAT1, MX1, and OASL. Finally, we demonstrated that the MEK/ERK signaling pathway was involved in the expression of SOCS3 mediated by NDV infection and V protein transfection, and using specific inhibitor U0126 to block this signaling pathway attenuated SOCS3 expression and inhibited NDV replication through promoting the expression of type I interferon, OASL and MX1. Taken together, these data demonstrate that NDV infection and NDV nonstructural V protein activates the expression of SOCS3 at the mRNA and protein level through a mechanism dependent on the MEK/ERK signaling pathway, which benefits virus replication.https://www.frontiersin.org/article/10.3389/fcimb.2019.00317/fullNewcastle disease virusSOCS3V proteinMEK/ERK pathwayviral replication
collection DOAJ
language English
format Article
sources DOAJ
author Xiangwei Wang
Yanqing Jia
Juan Ren
Na Huo
Haijin Liu
Sa Xiao
Xinglong Wang
Zengqi Yang
spellingShingle Xiangwei Wang
Yanqing Jia
Juan Ren
Na Huo
Haijin Liu
Sa Xiao
Xinglong Wang
Zengqi Yang
Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
Frontiers in Cellular and Infection Microbiology
Newcastle disease virus
SOCS3
V protein
MEK/ERK pathway
viral replication
author_facet Xiangwei Wang
Yanqing Jia
Juan Ren
Na Huo
Haijin Liu
Sa Xiao
Xinglong Wang
Zengqi Yang
author_sort Xiangwei Wang
title Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
title_short Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
title_full Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
title_fullStr Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
title_full_unstemmed Newcastle Disease Virus Nonstructural V Protein Upregulates SOCS3 Expression to Facilitate Viral Replication Depending on the MEK/ERK Pathway
title_sort newcastle disease virus nonstructural v protein upregulates socs3 expression to facilitate viral replication depending on the mek/erk pathway
publisher Frontiers Media S.A.
series Frontiers in Cellular and Infection Microbiology
issn 2235-2988
publishDate 2019-09-01
description Newcastle disease virus (NDV) causes serious economic losses to the poultry industry. In our previous study, we found that NDV induced a strong innate immune response in the chicken embryo and bursa of Fabricius (BF). However, the underlying mechanisms by which NDV escapes the host innate immunity are not well-understood. The suppressor of cytokine signaling 3 (SOCS3) inhibits the type I interferon-dependent antiviral signaling pathway by utilizing a feedback loop. In this study, we analyzed the transcriptome data of the chicken embryo and BF infected with NDV and found significant upregulation of SOCS3. Next, we demonstrated that NDV infection and nonstructural V protein induced the up-regulation of SOCS3. Furthermore, we showed that overexpression of SOCS3 facilitated viral replication and reduced the expression of phosphorylation STAT1, MX1, and OASL, while inhibition of SOCS3 with siRNAs reduced virus replication and promoted the expression of phosphorylation STAT1, MX1, and OASL. Finally, we demonstrated that the MEK/ERK signaling pathway was involved in the expression of SOCS3 mediated by NDV infection and V protein transfection, and using specific inhibitor U0126 to block this signaling pathway attenuated SOCS3 expression and inhibited NDV replication through promoting the expression of type I interferon, OASL and MX1. Taken together, these data demonstrate that NDV infection and NDV nonstructural V protein activates the expression of SOCS3 at the mRNA and protein level through a mechanism dependent on the MEK/ERK signaling pathway, which benefits virus replication.
topic Newcastle disease virus
SOCS3
V protein
MEK/ERK pathway
viral replication
url https://www.frontiersin.org/article/10.3389/fcimb.2019.00317/full
work_keys_str_mv AT xiangweiwang newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT yanqingjia newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT juanren newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT nahuo newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT haijinliu newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT saxiao newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT xinglongwang newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
AT zengqiyang newcastlediseasevirusnonstructuralvproteinupregulatessocs3expressiontofacilitateviralreplicationdependingonthemekerkpathway
_version_ 1724965748170817536