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The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact

The success of poxviruses as pathogens depends on their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation....

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Detalles Bibliográficos
Autores principales: Peauroi, Elise M., Carro, Stephen D., Pei, Luxin, Reynoso, Glennys V., Hickman, Heather D., Eisenlohr, Laurence C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678732/
https://www.ncbi.nlm.nih.gov/pubmed/36425759
http://dx.doi.org/10.1016/j.isci.2022.105510
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author Peauroi, Elise M.
Carro, Stephen D.
Pei, Luxin
Reynoso, Glennys V.
Hickman, Heather D.
Eisenlohr, Laurence C.
author_facet Peauroi, Elise M.
Carro, Stephen D.
Pei, Luxin
Reynoso, Glennys V.
Hickman, Heather D.
Eisenlohr, Laurence C.
author_sort Peauroi, Elise M.
collection PubMed
description The success of poxviruses as pathogens depends on their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production or the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node.
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spelling pubmed-96787322022-11-23 The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact Peauroi, Elise M. Carro, Stephen D. Pei, Luxin Reynoso, Glennys V. Hickman, Heather D. Eisenlohr, Laurence C. iScience Article The success of poxviruses as pathogens depends on their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production or the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node. Elsevier 2022-11-04 /pmc/articles/PMC9678732/ /pubmed/36425759 http://dx.doi.org/10.1016/j.isci.2022.105510 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Peauroi, Elise M.
Carro, Stephen D.
Pei, Luxin
Reynoso, Glennys V.
Hickman, Heather D.
Eisenlohr, Laurence C.
The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title_full The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title_fullStr The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title_full_unstemmed The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title_short The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact
title_sort ectromelia virus virulence factor c15 facilitates early viral spread by inhibiting nk cell contact
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678732/
https://www.ncbi.nlm.nih.gov/pubmed/36425759
http://dx.doi.org/10.1016/j.isci.2022.105510
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