RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.20.465121
DO 10.1101/2021.10.20.465121
A1 Daniela Niemeyer
A1 Simon Schroeder
A1 Kirstin Friedmann
A1 Friderike Weege
A1 Jakob Trimpert
A1 Anja Richter
A1 Saskia Stenzel
A1 Jenny Jansen
A1 Jackson Emanuel
A1 Julia Kazmierski
A1 Fabian Pott
A1 Lara M. Jeworowski
A1 Ruth Olmer
A1 Mark-Christian Jaboreck
A1 Beate Tenner
A1 Jan Papies
A1 Julian Heinze
A1 Felix Walper
A1 Marie L. Schmidt
A1 Nicolas Heinemann
A1 Elisabeth Möncke-Buchner
A1 Talitha Veith
A1 Morris Baumgardt
A1 Karen Hoffmann
A1 Marek Widera
A1 Tran Thi Nhu Thao
A1 Anita Balázs
A1 Jessica Schulze
A1 Christin Mache
A1 Markus Morkel
A1 Sandra Ciesek
A1 Leif G. Hanitsch
A1 Marcus A. Mall
A1 Andreas C. Hocke
A1 Volker Thiel
A1 Klaus Osterrieder
A1 Thorsten Wolff
A1 Ulrich Martin
A1 Victor M. Corman
A1 Marcel A. Müller
A1 Christine Goffinet
A1 Christian Drosten
YR 2021
UL http://biorxiv.org/content/early/2021/10/20/2021.10.20.465121.abstract
AB 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.Competing Interest StatementTechnische Universitaet Berlin, Freie Universitaet Berlin and Charite - Universitaetsmedizin have filed a patent application for siRNAs inhibiting SARS-CoV-2 replication with DN as co-author. MAMue and VMC are named together with Charite - Universitaetsmedizin Berlin and Euroimmun Medizinische Labordiagnostika AG on a patent application (EP3715847) filed recently regarding the diagnostic of SARS-CoV-2 by antibody testing. The other authors declare no competing interests.