Murine cytomegalovirus degrades MHC class II to colonize the salivary glands.
Cytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells of immunocompetent hosts. Persistence implies immune evasion, and CMVs evade CD8+ T cells by inhibiting MHC class I-restricted antigen presentation. Myeloid cells can also interact with CD4+ T cells via MHC class II (MHC...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1006905 |
| _version_ | 1831521414384975872 |
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| author | Joseph Yunis Helen E Farrell Kimberley Bruce Clara Lawler Stine Sidenius Orry Wyer Nicholas Davis-Poynter Philip G Stevenson |
| author_facet | Joseph Yunis Helen E Farrell Kimberley Bruce Clara Lawler Stine Sidenius Orry Wyer Nicholas Davis-Poynter Philip G Stevenson |
| author_sort | Joseph Yunis |
| collection | DOAJ |
| description | Cytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells of immunocompetent hosts. Persistence implies immune evasion, and CMVs evade CD8+ T cells by inhibiting MHC class I-restricted antigen presentation. Myeloid cells can also interact with CD4+ T cells via MHC class II (MHC II). Human CMV (HCMV) attacks the MHC II presentation pathway in vitro, but what role this evasion might play in host colonization is unknown. We show that Murine CMV (MCMV) down-regulates MHC II via M78, a multi-membrane spanning viral protein that captured MHC II from the cell surface and was necessary although not sufficient for its degradation in low pH endosomes. M78-deficient MCMV down-regulated MHC I but not MHC II. After intranasal inoculation, it showed a severe defect in salivary gland colonization that was associated with increased MHC II expression on infected cells, and was significantly rescued by CD4+ T cell loss. Therefore MCMV requires CD4+ T cell evasion by M78 to colonize the salivary glands, its main site of long-term shedding. |
| first_indexed | 2024-12-13T17:54:40Z |
| format | Article |
| id | doaj.art-a477f84d88f14c70bec7e05b40831c14 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T17:54:40Z |
| publishDate | 2018-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a477f84d88f14c70bec7e05b40831c142022-12-21T23:36:24ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-02-01142e100690510.1371/journal.ppat.1006905Murine cytomegalovirus degrades MHC class II to colonize the salivary glands.Joseph YunisHelen E FarrellKimberley BruceClara LawlerStine SideniusOrry WyerNicholas Davis-PoynterPhilip G StevensonCytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells of immunocompetent hosts. Persistence implies immune evasion, and CMVs evade CD8+ T cells by inhibiting MHC class I-restricted antigen presentation. Myeloid cells can also interact with CD4+ T cells via MHC class II (MHC II). Human CMV (HCMV) attacks the MHC II presentation pathway in vitro, but what role this evasion might play in host colonization is unknown. We show that Murine CMV (MCMV) down-regulates MHC II via M78, a multi-membrane spanning viral protein that captured MHC II from the cell surface and was necessary although not sufficient for its degradation in low pH endosomes. M78-deficient MCMV down-regulated MHC I but not MHC II. After intranasal inoculation, it showed a severe defect in salivary gland colonization that was associated with increased MHC II expression on infected cells, and was significantly rescued by CD4+ T cell loss. Therefore MCMV requires CD4+ T cell evasion by M78 to colonize the salivary glands, its main site of long-term shedding.https://doi.org/10.1371/journal.ppat.1006905 |
| spellingShingle | Joseph Yunis Helen E Farrell Kimberley Bruce Clara Lawler Stine Sidenius Orry Wyer Nicholas Davis-Poynter Philip G Stevenson Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. PLoS Pathogens |
| title | Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. |
| title_full | Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. |
| title_fullStr | Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. |
| title_full_unstemmed | Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. |
| title_short | Murine cytomegalovirus degrades MHC class II to colonize the salivary glands. |
| title_sort | murine cytomegalovirus degrades mhc class ii to colonize the salivary glands |
| url | https://doi.org/10.1371/journal.ppat.1006905 |
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