Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor
Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor
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Date
2019-07-09
Authors
Liu, Xiaoyang
Palaniyandi, Senthilkumar
Zhu, Iowis
Tang, Jin
Li, Weizhong
Wu, Xiaoling
Ochsner, Susan Park
Pauza, C. David
Cohen, Jeffrey I.
Zhu, Xiaoping
Advisor
Citation
Liu, 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-y
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Abstract
Human 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.
Notes
Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.