SARS-CoV-2 shifts transcription of host gene to increase Spike acylation and boost infectivity

Author:

Goot F. van der1ORCID,Mesquita Francisco Sarmento1,Abrami Laurence2ORCID,Bracq Lucie1,Panyain Nattawadee1,Mercier Vincent3,Kunz Béatrice1,Chuat Audrey1,Carlevaro-Fita Joana1,Trono Didier4ORCID

Affiliation:

1. Global Health Institute, School of Life Sciences, EPFL

2. School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL)

3. University of Geneva

4. Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences

Abstract

Abstract SARS-CoV-2 infection requires Spike protein mediating fusion between the viral and cellular membranes. The fusogenic activity of Spike requires its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Previous observations indicate that SARS-CoV-2 infection augments the S-acylation of Spike when compared to transfection. Here, we find that SARS-CoV-2 infection triggers a change in the transcriptional start site of the zddhc20 gene, both in cells and in an in vivo infection model, resulting in a 67-amino–acid-long N-terminally extended protein with 37-times higher Spike acylating activity, leading to enhanced viral infectivity. Furthermore, we observed the same induced transcriptional change in response to other challenges, such as chemically induced colitis, indicating that SARS-CoV-2 hijacks an existing cell damage response pathway to generate more infectious viruses.

Publisher

Research Square Platform LLC

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