Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor

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dc.contributor.authorLiu, Xiaoyang
dc.contributor.authorPalaniyandi, Senthilkumar
dc.contributor.authorZhu, Iowis
dc.contributor.authorTang, Jin
dc.contributor.authorLi, Weizhong
dc.contributor.authorWu, Xiaoling
dc.contributor.authorOchsner, Susan Park
dc.contributor.authorPauza, C. David
dc.contributor.authorCohen, Jeffrey I.
dc.contributor.authorZhu, Xiaoping
dc.date.accessioned2019-12-12T15:43:53Z
dc.date.available2019-12-12T15:43:53Z
dc.date.issued2019-07-09
dc.descriptionPartial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.
dc.description.abstractHuman cytomegalovirus (HCMV) can persistently infect humans, but how HCMV avoids humoral immunity is not clear. The neonatal Fc receptor (FcRn) controls IgG transport from the mother to the fetus and prolongs IgG half-life. Here we show that US11 inhibits the assembly of FcRn with β2m and retains FcRn in the endoplasmic reticulum (ER), consequently blocking FcRn trafficking to the endosome. Furthermore, US11 recruits the ubiquitin enzymes Derlin-1, TMEM129 and UbE2J2 to engage FcRn, consequently initiating the dislocation of FcRn from the ER to the cytosol and facilitating its degradation. Importantly, US11 inhibits IgGFcRn binding, resulting in a reduction of IgG transcytosis across intestinal or placental epithelial cells and IgG degradation in endothelial cells. Hence, these results identify the mechanism by which HCMV infection exploits an ER-associated degradation pathway through US11 to disable FcRn functions. These results have implications for vaccine development and immune surveillance.en_US
dc.identifierhttps://doi.org/10.13016/4lit-iqw8
dc.identifier.citationLiu, X., Palaniyandi, S., Zhu, I. et al. Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor. Nat Commun 10, 3020 (2019) doi:10.1038/s41467-019-10865-yen_US
dc.identifier.urihttp://hdl.handle.net/1903/25316
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isAvailableAtCollege of Agriculture & Natural Resourcesen_us
dc.relation.isAvailableAtDepartment of Veterinary Medicineen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectimmune evasionen_US
dc.subjectviral immune evasionen_US
dc.titleHuman cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptoren_US
dc.typeArticleen_US

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