Replication and single-cycle delivery of SARS-CoV-2 replicons

Author:

Ricardo-Lax Inna1ORCID,Luna Joseph M.1ORCID,Thao Tran Thi Nhu234,Le Pen Jérémie1ORCID,Yu Yingpu1ORCID,Hoffmann H.-Heinrich1ORCID,Schneider William M.1ORCID,Razooky Brandon S.1ORCID,Fernandez-Martinez Javier5ORCID,Schmidt Fabian6ORCID,Weisblum Yiska6ORCID,Trüeb Bettina Salome23,Berenguer Veiga Inês23ORCID,Schmied Kimberly23ORCID,Ebert Nadine23,Michailidis Eleftherios1ORCID,Peace Avery1ORCID,Sánchez-Rivera Francisco J.7ORCID,Lowe Scott W.7ORCID,Rout Michael P.5,Hatziioannou Theodora6,Bieniasz Paul D.6,Poirier John T.8ORCID,MacDonald Margaret R.1ORCID,Thiel Volker23ORCID,Rice Charles M.1ORCID

Affiliation:

1. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.

2. Institute of Virology and Immunology (IVI), Bern, Switzerland.

3. Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

4. Graduate School for Biomedical Science, University of Bern, Bern, Switzerland.

5. Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.

6. Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.

7. Cancer Biology and Genetics, MSKCC, New York, NY 10065, USA.

8. Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA.

Abstract

A tool to study SARS-CoV-2 Work with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires high-level biocontainment facilities, making it important to develop safer molecular tools that can potentially be used under less stringent conditions. Self-replicating RNAs known as replicons have long been used to study pathogenic RNA viruses; however, developing replicons to study SARS-SoV-2 has been challenging because of its large genome. Ricardo-Lax et al . used a yeast-based system to construct SARS-CoV-2 replicons that cannot assemble infectious virus because they lack the spike protein required for host cell entry. Transfecting cells with a spike-expressing plasmid and separately with the replicon generates replicon delivery particles (RDPs) that are only capable of one cycle of infection. The replicons and the RDPs can be used in different contexts for drug screening, and viral assays. —VV

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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