Structural basis for Epstein–Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins

Sathiyamoorthy, Karthik; Hu, Yao Xiong; Möhl, Britta S.; Chen, Jia; Longnecker, Richard; Jardetzky, Theodore S.

doi:10.1038/ncomms13557

Title: Structural basis for Epstein–Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins

Journal Article · Thu Dec 08 00:00:00 EST 2016 · Nature Communications

DOI:https://doi.org/10.1038/ncomms13557· OSTI ID:1339648

^[1]; Hu, Yao Xiong ^[1]; Möhl, Britta S. ^[2]; Chen, Jia ^[2]; Longnecker, Richard ^[2]; Jardetzky, Theodore S. ^[1]

Stanford Univ. School of Medicine, CA (United States). Dept. of Structural Biology
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine. Dept. of Microbiology and Immunology

Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. For Epstein–Barr virus (EBV), gHgL/gp42 complexes bind HLA class II to activate membrane fusion with B cells, but gp42 inhibits fusion and entry into epithelial cells. To clarify the mechanism by which gp42 controls the cell specificity of EBV infection, in this paper we determined the structure of gHgL/gp42 complex bound to an anti-gHgL antibody (E1D1). The critical regulator of EBV tropism is the gp42 N-terminal domain, which tethers the HLA-binding domain to gHgL by wrapping around the exterior of three gH domains. Both the gp42 N-terminal domain and E1D1 selectively inhibit epithelial-cell fusion; however, they engage distinct surfaces of gHgL. Finally, these observations clarify key determinants of EBV host cell tropism.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Stanford Univ. School of Medicine, CA (United States); Northwestern Univ., Chicago, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States). National Inst. of Allergy and Infectious Diseases (NIAID). National Cancer Inst. (NCI). National Inst. of General Medical Sciences (NIGMS); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)

Grant/Contract Number:: AC02-76SF00515; AC02-06CH11357; AI119480; AI076183; CA117794; 085P1000817; P41GM103393

OSTI ID:: 1339648

Journal Information:: Nature Communications, Vol. 7; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 65 works

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