Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles

Author:

Cosset François-Loic1,Marianneau Philippe2,Verney Geraldine1,Gallais Fabrice2,Tordo Noel2,Pécheur Eve-Isabelle3,ter Meulen Jan4,Deubel Vincent25,Bartosch Birke1

Affiliation:

1. Université de Lyon, UCB-Lyon 1, IFR128, INSERM, U758, and Ecole Normale Supérieure de Lyon, Lyon F-69007, France

2. Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, IFR 128 BioSciences Gerland, Lyon Sud, Lyon, France

3. Institut de Biologie et Chimie des Protéines, CNRS, UMR 5086, Université Lyon 1, IFR 128 BioSciences Gerland, Lyon Sud, Lyon, France

4. Institute of Virology, Philipps University, Marburg, Germany

5. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

Abstract

ABSTRACT The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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