Abstract
AbstractEpstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.
Funder
Beijing Municipal Science and Technology Commission
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference68 articles.
1. de-Thé G., et al. Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study—a review. IARC Sci Publ, 3-16 (1975).
2. Young, L. S., Yap, L. F. & Murray, P. G. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat. Rev. Cancer 16, 789–802 (2016).
3. Cohen, J. I., Fauci, A. S., Varmus, H. & Nabel, G. J. Epstein-Barr virus: an important vaccine target for cancer prevention. Sci. Transl. Med. 3, 107fs107 (2011).
4. Young, L. S. & Dawson, C. W. Epstein-Barr virus and nasopharyngeal carcinoma. Chin. J. Cancer 33, 581–590 (2014).
5. Tan, R. et al. Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun. (Lond.) 40, 564–585 (2020).
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