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...

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Bibliographic Details
Published in:	PLoS pathogens 2018-02, Vol.14 (2), p.e1006905-e1006905
Main Authors:	Yunis, Joseph, Farrell, Helen E, Bruce, Kimberley, Lawler, Clara, Sidenius, Stine, Wyer, Orry, Davis-Poynter, Nicholas, Stevenson, Philip G
Format:	Article
Language:	eng
Subjects:	Antigen presentation Biology and Life Sciences CD4 antigen CD8 antigen Cell surface Childrens health Colonization Cytomegalovirus Cytomegalovirus infections Cytomegaloviruses Development and progression Endosomes Genes Glands Health aspects Host-virus relationships Infections Inoculation Kinases Lymphocytes Lymphocytes T Major histocompatibility complex Medical research Medicine and Health Sciences Membrane proteins Myeloid cells Physiological aspects Proteins Research and Analysis Methods Salivary gland Salivary glands Vaccines Viral research Virus research
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Summary:	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.
ISSN:	1553-7374 1553-7366 1553-7374