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 language | English (US) |
|---|---|
| Pages (from-to) | 923-928 |
| Number of pages | 6 |
| Journal | Science |
| Volume | 356 |
| Issue number | 6341 |
| DOIs | |
| State | Published - Jun 2 2017 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
- General
Cite this
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 journal › Article
}
TY - JOUR
T1 - Structural basis for antibody-mediated neutralization of Lassa virus
AU - Hastie, Kathryn M.
AU - Zandonatti, Michelle A.
AU - Kleinfelter, Lara M.
AU - Heinrich, Megan L.
AU - Rowland, Megan M.
AU - Chandran, Kartik
AU - Branco, Luis M.
AU - Robinson, James E.
AU - Garry, Robert F.
AU - Saphire, Erica Ollmann
PY - 2017/6/2
Y1 - 2017/6/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020251761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020251761&partnerID=8YFLogxK
U2 - 10.1126/science.aam7260
DO - 10.1126/science.aam7260
M3 - Article
C2 - 28572385
AN - SCOPUS:85020251761
VL - 356
SP - 923
EP - 928
JO - Science
JF - Science
SN - 0036-8075
IS - 6341
ER -