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Pathogens 2019, 8(1), 1; https://doi.org/10.3390/pathogens8010001

Identification of Residues in Lassa Virus Glycoprotein Subunit 2 That Are Critical for Protein Function

1
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
2
Department of Infectious Diseases, Department of Population Health, Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 November 2018 / Revised: 20 December 2018 / Accepted: 22 December 2018 / Published: 26 December 2018
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Abstract

Lassa virus (LASV) is an Old World arenavirus, endemic to West Africa, capable of causing hemorrhagic fever. Currently, there are no approved vaccines or effective antivirals for LASV. However, thorough understanding of the LASV glycoprotein and entry into host cells could accelerate therapeutic design. LASV entry is a two-step process involving the viral glycoprotein (GP). First, the GP subunit 1 (GP1) binds to the cell surface receptor and the viral particle is engulfed into an endosome. Next, the drop in pH triggers GP rearrangements, which ultimately leads to the GP subunit 2 (GP2) forming a six-helix-bundle (6HB). The process of GP2 forming 6HB fuses the lysosomal membrane with the LASV envelope, allowing the LASV genome to enter the host cell. The aim of this study was to identify residues in GP2 that are crucial for LASV entry. To achieve this, we performed alanine scanning mutagenesis on GP2 residues. We tested these mutant GPs for efficient GP1-GP2 cleavage, cell-to-cell membrane fusion, and transduction into cells expressing α-dystroglycan and secondary LASV receptors. In total, we identified seven GP2 mutants that were cleaved efficiently but were unable to effectively transduce cells: GP-L280A, GP-L285A/I286A, GP-I323A, GP-L394A, GP-I403A, GP-L415A, and GP-R422A. Therefore, the data suggest these residues are critical for GP2 function in LASV entry. View Full-Text
Keywords: Lassa virus; arenavirus; viral glycoprotein; viral entry; viral fusion; fusion protein Lassa virus; arenavirus; viral glycoprotein; viral entry; viral fusion; fusion protein
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Willard, K.A.; Alston, J.T.; Acciani, M.; Brindley, M.A. Identification of Residues in Lassa Virus Glycoprotein Subunit 2 That Are Critical for Protein Function. Pathogens 2019, 8, 1.

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