4D-DIA-Based Quantitative Proteomic Analysis Reveals the Involvement of TRPV2 Protein in Duck Tembusu Virus Replication DOI Creative Commons

Chen Ji-min,

Fan Yang,

Lianjie Lai

и другие.

Viruses, Год журнала: 2024, Номер 16(12), С. 1831 - 1831

Опубликована: Ноя. 26, 2024

Duck Tembusu virus (DTMUV), a novel positive-sense RNA virus, has caused significant economic losses in the poultry industry of Eastern and Southeast Asia since its outbreak 2010. Furthermore, rapid transmission potential zoonotic nature DTMUV pose threat to public health safety. In this study, 4D-DIA quantitative proteomics approach was employed identify differentially expressed cellular proteins DTMUV-infected DF-1 cells, which are routinely used for isolation identification DTMUV, as well development vaccines against other viruses. One hundred fifty-seven were identified, including 84 upregulated 73 downregulated at 48 h post-infection, among CXCL8, DDX3X, TRPV2 may play crucial roles viral propagation. Notably, protein TRPV2, replication inhibited TRPV2-low-expressing cells. summary, our research represents application analyze proteomic landscape These findings provide valuable insights into understanding interaction mechanism between disease-resistant host factors breeding research.

Язык: Английский

The art of hijacking: how Nsp1 impacts host gene expression during coronaviral infections DOI Creative Commons
Evangelos D. Karousis

Biochemical Society Transactions, Год журнала: 2024, Номер 52(1), С. 481 - 490

Опубликована: Фев. 22, 2024

Non-structural protein 1 (Nsp1) is one of the first proteins produced during coronaviral infections. It plays a pivotal role in hijacking and rendering host gene expression under service virus. With focus on SARS-CoV-2, this review presents how Nsp1 selectively inhibits synthesis induces mRNA degradation but not viral mRNAs blocks nuclear export. The clinical implications are highlighted by showcasing pathogenic through repression interferon pathways features variants with mutations coding sequence. ability SARS-CoV-2 to hinder immune responses at an early step, absence homology any human proteins, availability structural information render ideal drug target therapeutic potential.

Язык: Английский

Процитировано

5

Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines DOI Creative Commons
David M. Renner, Nicholas A. Parenti, Nicole Bracci

и другие.

Viruses, Год журнала: 2025, Номер 17(1), С. 120 - 120

Опубликована: Янв. 16, 2025

The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area research to prepare for future viral emergence. We utilized three betacoronaviruses, one from each subgenus—HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)—, study interactions with PKR-like ER kinase (PERK) pathway integrated stress response (ISR)/unfolded protein (UPR). PERK becomes activated by an abundance unfolded proteins within endoplasmic reticulum (ER), leading phosphorylation eIF2α translational attenuation. demonstrate that MERS-CoV, HCoV-OC43, all activate induce responses downstream p-eIF2α, while only induces detectable p-eIF2α during infection. Using small molecule inhibitor dephosphorylation, we provide evidence HCoV-OC43 maximize replication through dephosphorylation. Interestingly, genetic ablation growth arrest DNA damage-inducible (GADD34) expression, inducible phosphatase 1 (PP1)-interacting partner targeting did not significantly alter or replication, siRNA knockdown constitutive PP1 partner, repressor (CReP), dramatically reduced replication. Combining GADD34 knockout CReP had maximum impact on was unaffected. Overall, conclude dephosphorylation is efficient production SARS-CoV-2, however, appears be insensitive and, infection, may even downregulate limit host translation.

Язык: Английский

Процитировано

0

The transcriptional and translational landscape of HCoV-OC43 infection DOI Creative Commons
Stefan Bresson,

Emanuela Sani,

Alicja Armatowska

и другие.

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012831 - e1012831

Опубликована: Янв. 27, 2025

The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of common cold. Here, we generated high-resolution atlas transcriptional translational landscape OC43 during time course following infection lung fibroblasts. Using ribosome profiling, quantified relative expression canonical open reading frames (ORFs) identified previously unannotated ORFs. These included several potential short upstream ORFs putative ORF nested inside M gene. In parallel, analyzed cellular response to infection. Endoplasmic reticulum (ER) stress genes were transcriptionally translationally induced beginning 12 18 hours post infection, respectively. By contrast, conventional antiviral mostly remained quiescent. At same points, observed accumulation increased translation noncoding transcripts normally targeted by nonsense mediated decay (NMD), suggesting NMD suppressed This work provides resources for deeper understanding gene responses

Язык: Английский

Процитировано

0

SARS-CoV-2 Nsp1-Resistant Modified RNA for the Creation of Nsp1-Responsive Systems DOI

Malvin Leonardo Pardi,

Kazuo Takayama, Hirohide Saito

и другие.

ACS Synthetic Biology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 5, 2025

Modified RNA (modRNA) facilitates the introduction of complex synthetic genetic circuits into cells without risk genomic integration, opening up implementation as therapeutics. However, number protein-RNA interfaces that are suitable for construction protein-responsive modRNA switches well lack exclusive selector systems stifles development RNA-based circuits. Here, we present creation a capable resisting effects Nsp1 reliable expression its coding sequence. Using both subgenomic viral 5'UTR and two modified nucleosides, observed efficient exogenous protein even in Nsp1-transfected cells. To demonstrate utility, developed barnase-barstar system conditional transcript suppression presence Nsp1. Altogether, resistance to Nsp1-mediated translational resulting Nsp1-sensing this study provide an invaluable opportunity develop new class protein-sensing more

Язык: Английский

Процитировано

0

SARS-CoV-2 Nsp1 traps RNA in the nucleus to escape immune detection DOI
Jaresley V. Guillen, Britt A. Glaunsinger

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(25)

Опубликована: Июнь 6, 2024

Язык: Английский

Процитировано

0

Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung Derived Cell Lines DOI Creative Commons
David M. Renner, Nicholas A. Parenti, Susan R. Weiss

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

The betacoronavirus genus contains five of the seven human viruses, making it a particularly critical area research to prepare for future viral emergence. We utilized three betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus) and MERS-CoV (merbecovirus)- study interaction with PKR-like ER kinase (PERK) pathway integrated stress response (ISR)/unfolded protein (UPR). PERK becomes activated by an abundance unfolded proteins within endoplasmic reticulum (ER), leading phosphorylation eIF2α translational attenuation in lung derived cell lines. demonstrate that MERS-CoV, HCoV-OC43, all activate induce responses downstream p-eIF2α, while only induces detectable p-eIF2α during infection. Using small molecule inhibitor dephosphorylation, we provide evidence HCoV-OC43 maximize replication through dephosphorylation. Interestingly, genetic ablation GADD34 expression, inducible phosphatase 1 (PP1)-interacting partner targeting did not significantly alter or replication, siRNA knockdown constitutive PP1 partner, CReP, dramatically reduced replication. Combining growth arrest DNA damage-inducible (GADD34) knockout peripheral membrane-targeted (CReP) had maximum impact on was unaffected. Overall, conclude dephosphorylation is efficient production SARS-CoV-2, however, appears be insensitive and, infection, may even downregulate limit host translation.

Язык: Английский

Процитировано

0

4D-DIA-Based Quantitative Proteomic Analysis Reveals the Involvement of TRPV2 Protein in Duck Tembusu Virus Replication DOI Creative Commons

Chen Ji-min,

Fan Yang,

Lianjie Lai

и другие.

Viruses, Год журнала: 2024, Номер 16(12), С. 1831 - 1831

Опубликована: Ноя. 26, 2024

Duck Tembusu virus (DTMUV), a novel positive-sense RNA virus, has caused significant economic losses in the poultry industry of Eastern and Southeast Asia since its outbreak 2010. Furthermore, rapid transmission potential zoonotic nature DTMUV pose threat to public health safety. In this study, 4D-DIA quantitative proteomics approach was employed identify differentially expressed cellular proteins DTMUV-infected DF-1 cells, which are routinely used for isolation identification DTMUV, as well development vaccines against other viruses. One hundred fifty-seven were identified, including 84 upregulated 73 downregulated at 48 h post-infection, among CXCL8, DDX3X, TRPV2 may play crucial roles viral propagation. Notably, protein TRPV2, replication inhibited TRPV2-low-expressing cells. summary, our research represents application analyze proteomic landscape These findings provide valuable insights into understanding interaction mechanism between disease-resistant host factors breeding research.

Язык: Английский

Процитировано

0