Structural basis for antibody-mediated neutralization of Lassa virus

Kathryn M. Hastie, Michelle A. Zandonatti, Lara M. Kleinfelter, Megan L. Heinrich, Megan M. Rowland, Kartik Chandran, Luis M. Branco, James E. Robinson, Robert F. Garry, Erica Ollmann Saphire

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.

Original languageEnglish (US)
Pages (from-to)923-928
Number of pages6
JournalScience
Volume356
Issue number6341
DOIs
StatePublished - Jun 2 2017

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Lassa virus
Arenavirus
Glycoproteins
Western Africa
Antibodies
Neutralizing Antibodies
Fever
Vaccines
Antigens

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Hastie, K. M., Zandonatti, M. A., Kleinfelter, L. M., Heinrich, M. L., Rowland, M. M., Chandran, K., ... Saphire, E. O. (2017). Structural basis for antibody-mediated neutralization of Lassa virus. Science, 356(6341), 923-928. https://doi.org/10.1126/science.aam7260

Structural basis for antibody-mediated neutralization of Lassa virus. / Hastie, Kathryn M.; Zandonatti, Michelle A.; Kleinfelter, Lara M.; Heinrich, Megan L.; Rowland, Megan M.; Chandran, Kartik; Branco, Luis M.; Robinson, James E.; Garry, Robert F.; Saphire, Erica Ollmann.

In: Science, Vol. 356, No. 6341, 02.06.2017, p. 923-928.

Research output: Contribution to journalArticle

Hastie, KM, Zandonatti, MA, Kleinfelter, LM, Heinrich, ML, Rowland, MM, Chandran, K, Branco, LM, Robinson, JE, Garry, RF & Saphire, EO 2017, 'Structural basis for antibody-mediated neutralization of Lassa virus', Science, vol. 356, no. 6341, pp. 923-928. https://doi.org/10.1126/science.aam7260
Hastie KM, Zandonatti MA, Kleinfelter LM, Heinrich ML, Rowland MM, Chandran K et al. Structural basis for antibody-mediated neutralization of Lassa virus. Science. 2017 Jun 2;356(6341):923-928. https://doi.org/10.1126/science.aam7260
Hastie, Kathryn M. ; Zandonatti, Michelle A. ; Kleinfelter, Lara M. ; Heinrich, Megan L. ; Rowland, Megan M. ; Chandran, Kartik ; Branco, Luis M. ; Robinson, James E. ; Garry, Robert F. ; Saphire, Erica Ollmann. / Structural basis for antibody-mediated neutralization of Lassa virus. In: Science. 2017 ; Vol. 356, No. 6341. pp. 923-928.
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