ZBTB7A promotes virus-host homeostasis during human coronavirus 229E infection

Xinyu Zhu; Joseph D Trimarco; Courtney A Williams; Alejandro Barrera; Timothy E Reddy; Nicholas S Heaton

doi:10.1016/j.celrep.2022.111540

ZBTB7A promotes virus-host homeostasis during human coronavirus 229E infection

Cell Rep. 2022 Oct 25;41(4):111540. doi: 10.1016/j.celrep.2022.111540. Epub 2022 Oct 5.

Authors

Xinyu Zhu¹, Joseph D Trimarco¹, Courtney A Williams², Alejandro Barrera², Timothy E Reddy³, Nicholas S Heaton⁴

Affiliations

¹ Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.
² Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
³ Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
⁴ Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. Electronic address: nicholas.heaton@duke.edu.

Abstract

The cellular fate after infection with human coronaviruses (HCoVs) is typically death. Previous data suggest, however, that the transcriptional state of an individual cell may sometimes allow additional outcomes of infection. Here, to probe the range of interactions a permissive cell type can have with a HCoV, we perform a CRISPR activation screen with HCoV-229E. The screen identified the transcription factor ZBTB7A, which strongly promotes cell survival after infection. Rather than suppressing viral infection, ZBTB7A upregulation allows the virus to induce a persistent infection and homeostatic state with the cell. We also find that control of oxidative stress is a primary driver of cellular survival during HCoV-229E infection. These data illustrate that, in addition to the nature of the infecting virus and the type of cell that it encounters, the cellular gene expression profile prior to infection can affect the eventual fate.

Keywords: CP: Microbiology; CRISPRa; cellular fate; oxidative stress; persistent infection.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Line, Tumor
Coronavirus 229E, Human* / genetics
DNA-Binding Proteins
Homeostasis
Humans
Transcription Factors / genetics

Substances

DNA-Binding Proteins
Transcription Factors
ZBTB7A protein, human