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

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.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [2] ;  [2] ;  [1]
  1. Stanford Univ. School of Medicine, CA (United States). Dept. of Structural Biology
  2. Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine. Dept. of Microbiology and Immunology
Publication Date:
Grant/Contract Number:
AC02-76SF00515; AC02-06CH11357; AI119480; AI076183; CA117794; 085P1000817; P41GM103393
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ. School of Medicine, CA (United States); Northwestern Univ., Chicago, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); 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)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; structural biology; virology
OSTI Identifier:
1339648