A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement
A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of ‘missing-self’ recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/38667 |
| _version_ | 1818019715217358848 |
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| author | Xiaoli Wang Sytse J Piersma Christopher A Nelson Ya-Nan Dai Ted Christensen Eric Lazear Liping Yang Marjolein Sluijter Thorbald van Hall Ted H Hansen Wayne M Yokoyama Daved H Fremont |
| author_facet | Xiaoli Wang Sytse J Piersma Christopher A Nelson Ya-Nan Dai Ted Christensen Eric Lazear Liping Yang Marjolein Sluijter Thorbald van Hall Ted H Hansen Wayne M Yokoyama Daved H Fremont |
| author_sort | Xiaoli Wang |
| collection | DOAJ |
| description | A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of ‘missing-self’ recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, pQa-1 selectively inhibits NKG2A+ NK cells and expression of pQa-1 can protect tumor cells from NK control in vivo. Collectively, these findings reveal an innovative NK evasion strategy wherein RHVP encodes a modified Qa-1 mimic refractory to MHC-I sabotage and capable of specifically engaging inhibitory receptors to circumvent NK activation. |
| first_indexed | 2024-04-14T07:55:06Z |
| format | Article |
| id | doaj.art-c9672d426e5e45eca7a97f1415a0cf7e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:55:06Z |
| publishDate | 2018-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c9672d426e5e45eca7a97f1415a0cf7e2022-12-22T02:05:04ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.38667A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagementXiaoli Wang0Sytse J Piersma1Christopher A Nelson2Ya-Nan Dai3Ted Christensen4Eric Lazear5Liping Yang6Marjolein Sluijter7Thorbald van Hall8https://orcid.org/0000-0002-9115-558XTed H Hansen9Wayne M Yokoyama10https://orcid.org/0000-0002-0566-7264Daved H Fremont11https://orcid.org/0000-0002-8544-2689Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDivision of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDivision of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Medical Oncology, Leiden University Medical Center (LUMC), Leiden, The NetherlandsDepartment of Medical Oncology, Leiden University Medical Center (LUMC), Leiden, The NetherlandsDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, United States; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United StatesA recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of ‘missing-self’ recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, pQa-1 selectively inhibits NKG2A+ NK cells and expression of pQa-1 can protect tumor cells from NK control in vivo. Collectively, these findings reveal an innovative NK evasion strategy wherein RHVP encodes a modified Qa-1 mimic refractory to MHC-I sabotage and capable of specifically engaging inhibitory receptors to circumvent NK activation.https://elifesciences.org/articles/38667viral immune evasionNK cell receptornon-classical MHC proteinmissing-self recognitionherpesvirus |
| spellingShingle | Xiaoli Wang Sytse J Piersma Christopher A Nelson Ya-Nan Dai Ted Christensen Eric Lazear Liping Yang Marjolein Sluijter Thorbald van Hall Ted H Hansen Wayne M Yokoyama Daved H Fremont A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement eLife viral immune evasion NK cell receptor non-classical MHC protein missing-self recognition herpesvirus |
| title | A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement |
| title_full | A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement |
| title_fullStr | A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement |
| title_full_unstemmed | A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement |
| title_short | A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement |
| title_sort | herpesvirus encoded qa 1 mimic inhibits natural killer cell cytotoxicity through cd94 nkg2a receptor engagement |
| topic | viral immune evasion NK cell receptor non-classical MHC protein missing-self recognition herpesvirus |
| url | https://elifesciences.org/articles/38667 |
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