The large groove found in the gH/gL structure is an important functional domain for epstein-barr virus fusion

Jia Chen, Theodore S. Jardetzky, Richard Longneckera*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins- gB, the gH/gL complex, and gp42-and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.

Original languageEnglish (US)
Pages (from-to)3620-3627
Number of pages8
JournalJournal of virology
Volume87
Issue number7
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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