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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Sushil Khatiwada, Gustavo Delhon, Sabal Chaulagain, Daniel L Rock
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