The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication

Jie Li; Qi Gui; Feng-Xia Liang; Joseph Sall; Qingyue Zhang; Yatong Duan; Avantika Dhabaria; Manor Askenazi; Beatrix Ueberheide; Kenneth A Stapleford; Michele Pagano

doi:10.1128/jvi.00507-23

The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication

J Virol. 2023 Oct 31;97(10):e0050723. doi: 10.1128/jvi.00507-23. Epub 2023 Sep 28.

Authors

Jie Li^#^{1

2}, Qi Gui^#^{1

2}, Feng-Xia Liang^{2

3}, Joseph Sall^{2

3}, Qingyue Zhang^{1

2}, Yatong Duan^{1

4}, Avantika Dhabaria⁵, Manor Askenazi^{1

6}, Beatrix Ueberheide^{1

2

5

7}, Kenneth A Stapleford⁸, Michele Pagano^{1

2

9}

Affiliations

¹ Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine , New York, New York, USA.
² Laura and Isaac Perlmutter NYU Cancer Center, New York University Grossman School of Medicine , New York, New York, USA.
³ Microscopy Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine , New York, New York, USA.
⁴ William A. Shine Great Neck South High School , Lake Success, New York, USA.
⁵ Proteomics Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine , New York, New York, USA.
⁶ Biomedical Hosting LLC , Arlington, Massachusetts, USA.
⁷ Department of Neurology, New York University Grossman School of Medicine , New York, New York, USA.
⁸ Department of Microbiology, New York University Grossman School of Medicine , New York, New York, USA.
⁹ Howard Hughes Medical Institute, New York University Grossman School of Medicine , New York, New York, USA.

^# Contributed equally.

Abstract

Generation of virus-host protein-protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination. Furthermore, REEP5/TRAM1 complex interacts with NSP3 at ROs and promotes viral replication. The significance of our research is identifying virus-host interactions that may be targeted for therapeutic intervention.

Keywords: ER membrane rearrangements; NSP3; REEP5; SARS-CoV-2; TRAM1; coronaviruses; replication organelle.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

COVID-19 / virology
Coronavirus Papain-Like Proteases* / metabolism
Host Microbial Interactions*
Humans
Membrane Glycoproteins* / metabolism
Membrane Proteins* / metabolism
Membrane Transport Proteins* / metabolism
Protein Binding
Protein Interaction Maps
SARS-CoV-2* / growth & development
SARS-CoV-2* / metabolism
Viral Nonstructural Proteins / metabolism
Virus Replication*

Substances

Membrane Glycoproteins
Membrane Proteins
Membrane Transport Proteins
NSP4 protein, SARS-CoV-2
NSP6 protein, SARS-CoV-2
papain-like protease, SARS-CoV-2
REEP5 protein, human
TRAM1 protein, human
Viral Nonstructural Proteins
Coronavirus Papain-Like Proteases

Abstract

Publication types

MeSH terms

Substances

Grants and funding