The novel ORFV protein ORFV113 activates LPA-p38 signaling.
Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G prot...
Guardado en:
Autores principales: | , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/42c2a4943461417a8be8a5a37aa4c811 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:42c2a4943461417a8be8a5a37aa4c811 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:42c2a4943461417a8be8a5a37aa4c8112021-12-02T20:00:04ZThe novel ORFV protein ORFV113 activates LPA-p38 signaling.1553-73661553-737410.1371/journal.ppat.1009971https://doaj.org/article/42c2a4943461417a8be8a5a37aa4c8112021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009971https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OV-IA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor.Sushil KhatiwadaGustavo DelhonSabal ChaulagainDaniel L RockPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1009971 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sushil Khatiwada Gustavo Delhon Sabal Chaulagain Daniel L Rock The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
description |
Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OV-IA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor. |
format |
article |
author |
Sushil Khatiwada Gustavo Delhon Sabal Chaulagain Daniel L Rock |
author_facet |
Sushil Khatiwada Gustavo Delhon Sabal Chaulagain Daniel L Rock |
author_sort |
Sushil Khatiwada |
title |
The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
title_short |
The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
title_full |
The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
title_fullStr |
The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
title_full_unstemmed |
The novel ORFV protein ORFV113 activates LPA-p38 signaling. |
title_sort |
novel orfv protein orfv113 activates lpa-p38 signaling. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/42c2a4943461417a8be8a5a37aa4c811 |
work_keys_str_mv |
AT sushilkhatiwada thenovelorfvproteinorfv113activateslpap38signaling AT gustavodelhon thenovelorfvproteinorfv113activateslpap38signaling AT sabalchaulagain thenovelorfvproteinorfv113activateslpap38signaling AT daniellrock thenovelorfvproteinorfv113activateslpap38signaling AT sushilkhatiwada novelorfvproteinorfv113activateslpap38signaling AT gustavodelhon novelorfvproteinorfv113activateslpap38signaling AT sabalchaulagain novelorfvproteinorfv113activateslpap38signaling AT daniellrock novelorfvproteinorfv113activateslpap38signaling |
_version_ |
1718375717241094144 |