Interference of SARS-CoV-2 on type Ⅰ IFN-mediated antiviral response DOI
Lai Wei

Опубликована: Сен. 7, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). Interferon's antiviral state is a key first line of defense against viral infection, but it weakened and delayed by SARSCoV- 2, making COVID-19 difficult to treat. This dysregulated innate immune response may contribute critical or even death. Thus, better control this virus deal with possible pandemics other coronaviruses in the future, we describe host's sensing systems for SARS-CoV-2 virus's tactics dodge response, including processes used proteins avoid interferon activation signaling host cells. We review evidence that proteins, specifically NSP1, 6, 13, ORF6 inhibit both induction interferon-induced ISGs. Moreover, highlight contradictory findings due different screening verifying systems. Finally, discussed whether blockade IFN could be overcome targeting antagonists restore interferon-mediated achieve cure.

Язык: Английский

Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies DOI Creative Commons
Mario Fragoso-Saavedra, Qiang Liu

Virology, Год журнала: 2025, Номер 604, С. 110412 - 110412

Опубликована: Янв. 19, 2025

Язык: Английский

Процитировано

0
Diversity of short linear interaction motifs in SARS-CoV-2 nucleocapsid protein DOI Creative Commons
Peter Schuck, Huaying Zhao

mBio, Год журнала: 2023, Номер 14(6)

Опубликована: Ноя. 29, 2023

ABSTRACT Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking cell processes. Here, we examine the role RNA virus sequence diversity in dynamics virus-host interface by analyzing uniquely vast record viable SARS-CoV-2 species with focus on multi-functional nucleocapsid protein. We observe abundant presentation encoding several essential protein interactions, alongside majority possibly non-functional randomly occurring motif sequences absent subsets species. A large number emerge ex nihilo through transient mutations relative to ancestral consensus sequence. The observed mutational landscape implies an accessible space that spans at least 25% known eukaryotic motifs. This reveals highly dynamic process capacity broadly explore motifs, allowing rapidly evolve interface. IMPORTANCE Short (SLiMs) are 3–10 amino acid long intrinsically disordered regions (IDRs) serve ubiquitous protein-protein modules cells. Through molecular mimicry, viruses hijack these control cellular It is thought small size SLiMs high mutation frequencies IDRs allow rapid adaptation. However, salient characteristic viruses, due replication errors, their obligate existence mutant swarms. Taking advantage genomic database SARS-CoV-2, here, analyze SLiMs, focusing abundant, find produces abundance transiently present allows efficiently host-virus

Язык: Английский

Процитировано

8
The Nucleocapsid Proteins of SARS-CoV-2 and Its Close Relative Bat Coronavirus RaTG13 Are Capable of Inhibiting PKR- and RNase L-Mediated Antiviral Pathways DOI Creative Commons

Kyle LeBlanc,

Jessie Lynch,

Christine Layne

и другие.

Microbiology Spectrum, Год журнала: 2023, Номер 11(3)

Опубликована: Май 8, 2023

Coronaviruses (CoVs), including severe acute respiratory syndrome CoV (SARS-CoV), Middle East (MERS-CoV), and SARS-CoV-2, produce double-stranded RNA (dsRNA) that activates antiviral pathways such as PKR OAS/RNase L. To successfully replicate in hosts, viruses must evade pathways. Currently, the mechanism of how SARS-CoV-2 antagonizes dsRNA-activated is unknown. In this study, we demonstrate nucleocapsid (N) protein, most abundant viral structural capable binding to dsRNA phosphorylated PKR, inhibiting both L The N protein bat coronavirus (bat-CoV) RaTG13, closest relative has a similar ability inhibit human RNase Via mutagenic analysis, found C-terminal domain (CTD) sufficient for activity. Interestingly, while CTD also inhibition activity requires not only but central linker region (LKR). Thus, our findings antagonizing two critical activated by its activities more than mediated CTD.

Язык: Английский

Процитировано

7
The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation DOI Creative Commons
Congcong Huang,

Yiping Yin,

Pan Pan

и другие.

Viruses, Год журнала: 2023, Номер 15(12), С. 2304 - 2304

Опубликована: Ноя. 24, 2023

Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with signaling, specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that N enhances interaction between human SUMO-conjugating enzyme UBC9 MAVS. Increased MAVS-UBC9 leads enhanced SUMOylation of MAVS, its ubiquitination, resulting inhibition phosphorylation events involving IKKα, TBK1, IRF3, thus disrupting signaling. highlights role modulating immune affecting MAVS ubiquitination processes, leading signaling pathway. These findings shed light on complex mechanisms utilized manipulate host’s antiviral defenses provide potential insights developing targeted therapeutic strategies against severe COVID-19.

Язык: Английский

Процитировано

6
Upregulation of Porcine Epidemic Diarrhea Virus (PEDV) RNA translation by the nucleocapsid protein DOI Creative Commons

Lin Hao,

Mario Fragoso-Saavedra, Qiang Liu

и другие.

Virology, Год журнала: 2024, Номер 602, С. 110306 - 110306

Опубликована: Ноя. 20, 2024

Язык: Английский

Процитировано

1
Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein DOI Open Access
Peter Schuck, Huaying Zhao

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 1, 2023

Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking cell processes. Here, we examine the role RNA-virus sequence diversity in dynamics virus-host interface, by analyzing uniquely vast record viable SARS-CoV-2 species with focus on multi-functional nucleocapsid protein. We observe abundant presentation encoding several essential protein interactions, alongside majority possibly non-functional randomly occurring motif sequences absent subsets virus species. A large number emerge

Язык: Английский

Процитировано

2
The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation DOI Open Access
Congcong Huang,

Yiping Yin,

Pan Pan

и другие.

Опубликована: Окт. 24, 2023

Severe COVID-19 patients show impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. The SARS-CoV-2 nucleocapsid protein has been implicated in inhibiting through interfering with signaling. This study reveals that enhances interaction between human SUMO-conjugating enzyme UBC9 MAVS. Increased MAVS-UBC9 leads enhanced SUMOylation of MAVS, its ubiquitination, resulting the inhibition phosphorylation events involving IKKα, TBK1, IRF3, disrupting These results provide essential insights into intricate regulation host's innate immunity during SARS-COV-2 invasion. Understanding these complex molecular mechanisms is crucial developing effective therapeutic interventions against potential future outbreaks.

Язык: Английский

Процитировано

1
Interference of SARS-CoV-2 on type Ⅰ IFN-mediated antiviral response DOI
Lai Wei

Опубликована: Сен. 7, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). Interferon's antiviral state is a key first line of defense against viral infection, but it weakened and delayed by SARSCoV- 2, making COVID-19 difficult to treat. This dysregulated innate immune response may contribute critical or even death. Thus, better control this virus deal with possible pandemics other coronaviruses in the future, we describe host's sensing systems for SARS-CoV-2 virus's tactics dodge response, including processes used proteins avoid interferon activation signaling host cells. We review evidence that proteins, specifically NSP1, 6, 13, ORF6 inhibit both induction interferon-induced ISGs. Moreover, highlight contradictory findings due different screening verifying systems. Finally, discussed whether blockade IFN could be overcome targeting antagonists restore interferon-mediated achieve cure.

Язык: Английский

Процитировано

0