Post-entry, spike-dependent replication advantage of B.1.1.7 and B.1.617.2 over B.1 SARS-CoV-2 in an ACE2-deficient human lung cell line

Autor: Jessica Schulze, Karen Hoffmann, Marek Widera, Daniela Niemeyer, Victor M. Corman, Fabian Pott, Simon Schroeder, Klaus Osterrieder, Friderike Weege, Christine Goffinet, Ruth Olmer, Sandra Ciesek, Thorsten Wolff, Morris Baumgardt, Julia Kazmierski, Felix Walper, Marcel A Mueller, Jackson Emanuel, Jenny Jansen, Lara Maria Jeworowski, Talitha Veith, Anita Balázs, Leif G. Hanitsch, Elisabeth Moencke-Buchner, Ulrich Martin, Markus Morkel, Christian Drosten, Christin Mache, Saskia Stenzel, Andreas C. Hocke, Beate Tenner, Anja Richter, Jan Papies, Mark-Christian Jaboreck, Marcus A. Mall, Volker Thiel, Marie Luisa Schmidt, Jakob Trimpert, Nicolas Heinemann, Tran Thi Nhu Thao, Julian Heinze, Kirstin Friedmann
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.10.20.465121
Popis: Epidemiological data demonstrate that SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.617.2 are more transmissible and infections are associated with a higher mortality than non-VOC virus infections. Phenotypic properties underlying their enhanced spread in the human population remain unknown. B.1.1.7 virus isolates displayed inferior or equivalent spread in most cell lines and primary cells compared to an ancestral B.1 SARS-CoV-2, and were outcompeted by the latter. Lower infectivity and delayed entry kinetics of B.1.1.7 viruses were accompanied by inefficient proteolytic processing of spike. B.1.1.7 viruses failed to escape from neutralizing antibodies, but slightly dampened induction of innate immunity. The bronchial cell line NCI-H1299 supported 24- and 595-fold increased growth of B.1.1.7 and B.1.617.2 viruses, respectively, in the absence of detectable ACE2 expression and in a spike-determined fashion. Superior spread in NCI-H1299 cells suggests that VOCs employ a distinct set of cellular cofactors that may be unavailable in standard cell lines.
Databáze: OpenAIRE