Molecular architecture of the human tRNA ligase complex DOI Creative Commons
Alena Kroupova, Fabian Ackle, Igor Asanović

и другие.

eLife, Год журнала: 2021, Номер 10

Опубликована: Дек. 2, 2021

RtcB enzymes are RNA ligases that play essential roles in tRNA splicing, unfolded protein response, and repair. In metazoa, functions as part of a five-subunit ligase complex (tRNA-LC) along with Ddx1, Cgi-99, Fam98B, Ashwin. The human tRNA-LC or its individual subunits have been implicated additional cellular processes including microRNA maturation, viral replication, DNA double-strand break repair, mRNA transport. Here, we present biochemical analysis the inter-subunit interactions within crystal structures catalytic subunit RTCB N-terminal domain CGI-99. We show core is assembled from C-terminal alpha-helical regions DDX1, CGI-99, FAM98B, all which required for integrity. CGI-99 displays structural homology to calponin-homology domains, FAM98B associate via their domains form stable subcomplex. structure GMP-bound reveals divalent metal coordination geometry active site, providing insights into mechanism. Collectively, these findings shed light on molecular architecture mechanism provide framework understanding metabolism.

Язык: Английский

Cellular host factors for SARS-CoV-2 infection DOI Creative Commons
Jim Baggen, Els Vanstreels, Sander Jansen

и другие.

Nature Microbiology, Год журнала: 2021, Номер 6(10), С. 1219 - 1232

Опубликована: Сен. 1, 2021

The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives and caused a global economic crisis. No effective antiviral drugs are currently available to treat infections severe acute respiratory syndrome 2 (SARS-CoV-2). medical need imposed by the spurred unprecedented research efforts study biology. Every virus depends on cellular host factors pathways for successful replication. These proviral represent attractive targets therapy as they genetically more stable than viral may be shared among related viruses. application various 'omics' technologies led rapid discovery that required completion SARS-CoV-2 life cycle. In this Review, we summarize insights into infection were mainly obtained using functional genetic interactome screens. We discuss processes important cycle, well parallels with non-coronaviruses. Finally, highlight could targeted clinically approved molecules in clinical trials potential therapies COVID-19. Proviral infection, replication COVID-19 reviewed.

Язык: Английский

Процитировано

189
The SARS-CoV-2 RNA interactome DOI Creative Commons
Sung‐Yul Lee, Young-Suk Lee, Yeon Choi

и другие.

Molecular Cell, Год журнала: 2021, Номер 81(13), С. 2838 - 2850.e6

Опубликована: Апрель 27, 2021

Язык: Английский

Процитировано

155
SARS-CoV-2 biology and host interactions DOI
Silvio Steiner, Annika Kratzel, G. Tuba Barut

и другие.

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(4), С. 206 - 225

Опубликована: Янв. 15, 2024

Язык: Английский

Процитировано

89
SARS-CoV-2 and the Host Cell: A Tale of Interactions DOI Creative Commons
Massimo Pizzato,

Chiara Baraldi,

Giulia Boscato Sopetto

и другие.

Frontiers in Virology, Год журнала: 2022, Номер 1

Опубликована: Янв. 12, 2022

The ability of a virus to spread between individuals, its replication capacity and the clinical course infection are macroscopic consequences multifaceted molecular interaction viral components with host cell. heavy impact COVID-19 on world population, economics sanitary systems calls for therapeutic prophylactic solutions that require deep characterization interactions occurring cells. Unveiling how SARS-CoV-2 engages factors throughout life cycle is therefore fundamental understand pathogenic mechanisms underlying design antiviral therapies strategies. Two years into pandemic, this review provides an overview interplay cell, focus machinery compartments pivotal cellular response. Starting cell surface, following replicative through entry pathways, survival in cytoplasm, egress from infected unravels complex network highlighting knowledge has potential set basis development innovative

Язык: Английский

Процитировано

72
SARS-CoV-2 and innate immunity: the good, the bad, and the “goldilocks” DOI Creative Commons
Benjamín L. Sievers, Mark T. K. Cheng,

Kata Csiba

и другие.

Cellular and Molecular Immunology, Год журнала: 2023, Номер 21(2), С. 171 - 183

Опубликована: Ноя. 20, 2023

Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.

Язык: Английский

Процитировано

51
Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection DOI Creative Commons
Jiakai Hou, Yanjun Wei, Jing Zou

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses multi-omics data screen, association studies, single-cell RNA-Seq, host-virus proteins or protein/RNA interactome. This study uncovers many that currently underappreciated, including components V-ATPases, ESCRT, N-glycosylation pathways modulate viral entry and/or replication. The cohesin complex is also identified as an pathway, suggesting important role three-dimensional chromatin organization mediating host-viral interaction. Furthermore, discover another regulator KLF5, transcriptional factor involved sphingolipid metabolism, which up-regulated, harbors genetic variations linked COVID-19 patients with severe symptoms. Anti-viral effects three candidates (DAZAP2/VTA1/KLF5) confirmed individually. Molecular characterization DAZAP2/VTA1/KLF5-knockout cells highlights involvement genes related coagulation system determining severity COVID-19. Together, our results provide further resources understanding network during may help develop new countermeasure strategies.

Язык: Английский

Процитировано

20
Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly DOI Creative Commons

Émilie Murigneux,

Laurent Softic,

C. Aubé

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 20, 2024

Язык: Английский

Процитировано

19
The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting DOI Creative Commons
Matthias M. Zimmer, Anuja Kibe, Ulfert Rand

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Дек. 10, 2021

Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral, structural and replicative enzymes that are encoded an alternative reading frame. Despite the importance PRF for viral life cycle, it still largely unknown how to what extent cellular factors alter mechanical properties frameshift elements thereby impact virulence. This prompted us comprehensively dissect interplay between SARS-CoV-2 element host proteome. We reveal short isoform zinc-finger antiviral protein (ZAP-S) direct regulator infected cells. ZAP-S overexpression strongly impairs inhibits replication. Using vitro ensemble single-molecule techniques, we further demonstrate directly interacts with RNA interferes folding element. Together, these data identify as host-encoded inhibitor expand our understanding RNA-based regulation.

Язык: Английский

Процитировано

80
Characterization and functional interrogation of the SARS-CoV-2 RNA interactome DOI Creative Commons

Athéna Labeau,

Luc Fery-Simonian, Alain Lefèvre‐Utile

и другие.

Cell Reports, Год журнала: 2022, Номер 39(4), С. 110744 - 110744

Опубликована: Апрель 1, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has led to a devastating global health crisis. The emergence variants that escape neutralizing responses emphasizes urgent need deepen our understanding SARS-CoV-2 biology. Using comprehensive identification RNA-binding proteins (RBPs) by mass spectrometry (ChIRP-MS) approach, we identify 107 high-confidence cellular factors interact with genome during infection. By systematically knocking down their expression in human lung epithelial cells, find majority identified RBPs are proviral factors. In particular, show HNRNPA2B1, ILF3, QKI, and SFPQ promote viral RNA amplification. Our study provides valuable resources for future investigations into mechanisms replication host-centered antiviral therapies.

Язык: Английский

Процитировано

54
A proteome-scale map of the SARS-CoV-2–human contactome DOI Creative Commons
Dae‐Kyum Kim, Benjamin Weller, Chung-Wen Lin

и другие.

Nature Biotechnology, Год журнала: 2022, Номер 41(1), С. 140 - 149

Опубликована: Окт. 10, 2022

Abstract Understanding the mechanisms of coronavirus disease 2019 (COVID-19) severity to efficiently design therapies for emerging virus variants remains an urgent challenge ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules host proteome, vast majority these virus–host (the ‘contactome’) have not been identified. Here, we present a systematic contactome map severe acute respiratory syndrome 2 (SARS-CoV-2) with human encompassing more than 200 binary intraviral protein–protein interactions. We find that proteins genetically associated comorbidities illness long COVID enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, demonstrate NSP14 activates nuclear factor κB (NF-κB)-dependent transcription, even presence cytokine signaling. Moreover, several tested proteins, genetic knock-down substantially reduces replication. Additionally, show USP25 this effect is phenocopied small-molecule inhibitor AZ1. Our results connect architecture COVID-19 offer potential therapeutic targets.

Язык: Английский

Процитировано

48