Cargando…
Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to q...
| Autores principales: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
eLife Sciences Publications, Ltd
2017
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367895/ https://www.ncbi.nlm.nih.gov/pubmed/28186488 http://dx.doi.org/10.7554/eLife.22206 |
| _version_ | 1782517850663026688 |
|---|---|
| author | Fielding, Ceri A Weekes, Michael P Nobre, Luis V Ruckova, Eva Wilkie, Gavin S Paulo, Joao A Chang, Chiwen Suárez, Nicolás M Davies, James A Antrobus, Robin Stanton, Richard J Aicheler, Rebecca J Nichols, Hester Vojtesek, Borek Trowsdale, John Davison, Andrew J Gygi, Steven P Tomasec, Peter Lehner, Paul J Wilkinson, Gavin W G |
| author_facet | Fielding, Ceri A Weekes, Michael P Nobre, Luis V Ruckova, Eva Wilkie, Gavin S Paulo, Joao A Chang, Chiwen Suárez, Nicolás M Davies, James A Antrobus, Robin Stanton, Richard J Aicheler, Rebecca J Nichols, Hester Vojtesek, Borek Trowsdale, John Davison, Andrew J Gygi, Steven P Tomasec, Peter Lehner, Paul J Wilkinson, Gavin W G |
| author_sort | Fielding, Ceri A |
| collection | PubMed |
| description | The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation. DOI: http://dx.doi.org/10.7554/eLife.22206.001 |
| format | Online Article Text |
| id | pubmed-5367895 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-53678952017-03-29 Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation Fielding, Ceri A Weekes, Michael P Nobre, Luis V Ruckova, Eva Wilkie, Gavin S Paulo, Joao A Chang, Chiwen Suárez, Nicolás M Davies, James A Antrobus, Robin Stanton, Richard J Aicheler, Rebecca J Nichols, Hester Vojtesek, Borek Trowsdale, John Davison, Andrew J Gygi, Steven P Tomasec, Peter Lehner, Paul J Wilkinson, Gavin W G eLife Immunology The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation. DOI: http://dx.doi.org/10.7554/eLife.22206.001 eLife Sciences Publications, Ltd 2017-02-10 /pmc/articles/PMC5367895/ /pubmed/28186488 http://dx.doi.org/10.7554/eLife.22206 Text en © 2017, Fielding et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
| spellingShingle | Immunology Fielding, Ceri A Weekes, Michael P Nobre, Luis V Ruckova, Eva Wilkie, Gavin S Paulo, Joao A Chang, Chiwen Suárez, Nicolás M Davies, James A Antrobus, Robin Stanton, Richard J Aicheler, Rebecca J Nichols, Hester Vojtesek, Borek Trowsdale, John Davison, Andrew J Gygi, Steven P Tomasec, Peter Lehner, Paul J Wilkinson, Gavin W G Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title | Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title_full | Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title_fullStr | Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title_full_unstemmed | Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title_short | Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| title_sort | control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation |
| topic | Immunology |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367895/ https://www.ncbi.nlm.nih.gov/pubmed/28186488 http://dx.doi.org/10.7554/eLife.22206 |
| work_keys_str_mv | AT fieldingceria controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT weekesmichaelp controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT nobreluisv controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT ruckovaeva controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT wilkiegavins controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT paulojoaoa controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT changchiwen controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT suareznicolasm controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT daviesjamesa controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT antrobusrobin controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT stantonrichardj controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT aichelerrebeccaj controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT nicholshester controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT vojtesekborek controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT trowsdalejohn controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT davisonandrewj controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT gygistevenp controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT tomasecpeter controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT lehnerpaulj controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation AT wilkinsongavinwg controlofimmuneligandsbymembersofacytomegalovirusgeneexpansionsuppressesnaturalkillercellactivation |