SARS-CoV-2 ORF3a induces COVID-19-associated kidney injury through HMGB1-mediated cytokine production DOI Creative Commons
Chen‐Yu Zhang,

Volodymyr Gerzanich,

Ruth Cruz‐Cosme

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(11)

Published: Sept. 30, 2024

ABSTRACT The primary challenge posed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19-related mortality, often exacerbated additional medical complications, such as COVID-19-associated kidney injuries (CAKIs). Up to half of COVID-19 patients experience with those facing failure and injury having the worst overall prognosis. Despite significant impact CAKI on mortality its enduring effects in long COVID, underlying causes molecular mechanisms remain elusive. In this study, we identified a functional relationship between expression SARS-CoV-2 ORF3a protein inflammation-driven apoptotic death renal tubular epithelial cells CAKI. We demonstrate vitro that independently induces cell-specific cell death, evidenced elevation molecule-1 (KIM-1) activation NF-kB-mediated proinflammatory cytokine (TNFα IL-6) production. By examining tissues SARS-CoV-2-infected K18-ACE2 transgenic mice, observed similar correlation ORF3a-induced cytopathic changes injury. This was further validated through reconstitution via direct adenoviral injection into mouse kidneys. Through medicinal analysis, natural compound, glycyrrhizin (GL4419), which not only blocks viral replication cells, but also mitigates inhibiting high mobility group box 1 (HMGB1) protein, leading reduction KIM-1. Moreover, interacts HMGB1. Overproduction or downregulation hmgb1 results correlative cellular KIM-1 response respective production, implicating crucial role HMGB1 ORF3a-inflicted injuries. Our data suggest link injury, highlighting unique therapeutic target contributing IMPORTANCE major during pandemic has tragically claimed millions lives. morbidity are pre-existing conditions, chronic diseases (CKDs), development (AKI) due COVID-19, collectively known Patients who have poorest clinical outcomes, including increased mortality. these alarming findings, there critical gap our understanding study establishes induced linking initially studies AKI animal studies, either expressing alone context infection. elucidating mechanistic pathways, research deepens presents potential avenues address healthcare challenges faced individuals conditions.

Language: Английский

Unraveling NbCML30-mediated defense against Sclerotinia sclerotiorum and Phytophthora capsici in Nicotiana benthamiana: A transcriptomic perspective DOI

Xiaoyan Wang,

Xingyi Luo,

Qin Wang

et al.

Physiological and Molecular Plant Pathology, Journal Year: 2024, Volume and Issue: 131, P. 102273 - 102273

Published: March 28, 2024

Language: Английский

Citations

0
Advanced Protocol for Molecular Characterization of Viral Genome in Fission Yeast (Schizosaccharomyces pombe) DOI Creative Commons
Jiantao Zhang, Zsigmond Benkő, Chen‐Yu Zhang

et al.

Pathogens, Journal Year: 2024, Volume and Issue: 13(7), P. 566 - 566

Published: July 4, 2024

Fission yeast, a single-cell eukaryotic organism, shares many fundamental cellular processes with higher eukaryotes, including gene transcription and regulation, cell cycle vesicular transport membrane trafficking, death resulting from the stress response. As result, fission yeast has proven to be versatile model organism for studying human physiology diseases such as dysregulation cancer, well autophagy neurodegenerative like Alzheimer’s, Parkinson’s, Huntington’s diseases. Given that viruses are obligate intracellular parasites rely on host machinery replicate produce, could serve surrogate identify viral proteins affect processes. This approach facilitate study of virus–host interactions help potential targets antiviral therapy. Using functional characterization genomes offers several advantages, well-characterized haploid genome, robustness, cost-effectiveness, ease maintenance, rapid doubling time. Therefore, emerges valuable system comprehensive proteins, aiding in identification therapeutic or impact highly conserved functions significant virologic implications. Importantly, this track record success various plant viruses. In protocol, we present streamlined scalable molecular cloning strategy tailored genome-wide yeast.

Language: Английский

Citations

0
SARS-CoV-2 ORF3a induces COVID-19-associated kidney injury through HMGB1-mediated cytokine production DOI Creative Commons
Chen‐Yu Zhang,

Volodymyr Gerzanich,

Ruth Cruz‐Cosme

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(11)

Published: Sept. 30, 2024

ABSTRACT The primary challenge posed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19-related mortality, often exacerbated additional medical complications, such as COVID-19-associated kidney injuries (CAKIs). Up to half of COVID-19 patients experience with those facing failure and injury having the worst overall prognosis. Despite significant impact CAKI on mortality its enduring effects in long COVID, underlying causes molecular mechanisms remain elusive. In this study, we identified a functional relationship between expression SARS-CoV-2 ORF3a protein inflammation-driven apoptotic death renal tubular epithelial cells CAKI. We demonstrate vitro that independently induces cell-specific cell death, evidenced elevation molecule-1 (KIM-1) activation NF-kB-mediated proinflammatory cytokine (TNFα IL-6) production. By examining tissues SARS-CoV-2-infected K18-ACE2 transgenic mice, observed similar correlation ORF3a-induced cytopathic changes injury. This was further validated through reconstitution via direct adenoviral injection into mouse kidneys. Through medicinal analysis, natural compound, glycyrrhizin (GL4419), which not only blocks viral replication cells, but also mitigates inhibiting high mobility group box 1 (HMGB1) protein, leading reduction KIM-1. Moreover, interacts HMGB1. Overproduction or downregulation hmgb1 results correlative cellular KIM-1 response respective production, implicating crucial role HMGB1 ORF3a-inflicted injuries. Our data suggest link injury, highlighting unique therapeutic target contributing IMPORTANCE major during pandemic has tragically claimed millions lives. morbidity are pre-existing conditions, chronic diseases (CKDs), development (AKI) due COVID-19, collectively known Patients who have poorest clinical outcomes, including increased mortality. these alarming findings, there critical gap our understanding study establishes induced linking initially studies AKI animal studies, either expressing alone context infection. elucidating mechanistic pathways, research deepens presents potential avenues address healthcare challenges faced individuals conditions.

Language: Английский

Citations

0