Mechanistic basis for potent neutralization of Sin Nombre hantavirus by a human monoclonal antibody.

Autor: Stass R; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Engdahl TB; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Chapman NS; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Wolters RM; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Handal LS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Diaz SM; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Crowe JE Jr; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org., Bowden TA; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. thomas.bowden@strubi.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 Jul; Vol. 8 (7), pp. 1293-1303. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1038/s41564-023-01413-y
Abstrakt: Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn-Gc) 4 glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn-Gc) 4 ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection.
(© 2023. The Author(s).)
Databáze: MEDLINE
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