Porcine Epidemic Diarrhea Virus nsp7 Inhibits MDA5 Dephosphorylation to Antagonize Type I Interferon Production DOI Creative Commons
Jian-Song Zhang, Puxian Fang,

Jie Ren

et al.

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(2)

Published: March 28, 2023

Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that causes high mortality in piglets and has catastrophic effects on the global pig industry. PEDV-encoded nonstructural protein 7 (nsp7) an important component of viral replication transcription complex, previous study reported it inhibits poly(I:C)-induced type I interferon (IFN) production, but mechanism by which this occurs remains unclear. Here, we demonstrated ectopic expression PEDV nsp7 antagonized Sendai (SeV)-induced beta (IFN-β) as well activation factors regulatory factor 3 (IRF3) nuclear factor-kappa B (NF-κB) both HEK-293T LLC-PK1 cells. Mechanistically, targets melanoma differentiation-associated gene 5 (MDA5) interacts with its caspase recruitment domains (CARDs), sequester interactions between MDA5 phosphatase 1 (PP1) catalytic subunits (PP1α PP1γ), thereby suppressing S828 dephosphorylation keeping inactive. Furthermore, infection attenuated multimerization MDA5-PP1α/-γ interactions. We also tested orthologs five other mammalian coronaviruses found all them except severe acute respiratory syndrome 2 (SARS-CoV-2) inhibited SeV- or MDA5-induced IFN-β production. Collectively, these results suggest inhibition may be common strategy employed some to antagonize MDA5-mediated IFN IMPORTANCE Since late 2010, porcine variant pathogenesis swept through most farms many countries, resulting significant economic losses. Coronavirus (nsp7), conserved within family Coronaviridae, combines nsp8 nsp12 form complex indispensable for replication. However, function largely unknown. Our present demonstrates specifically competes PP1 binding impedes PP1-mediated at S828, blocking revealing utilized efficiently escape host innate immunity.

Language: Английский

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

Citations

989
SARS-CoV-2 infection and persistence in the human body and brain at autopsy DOI Open Access
Sydney Stein, Sabrina Ramelli, Alison Grazioli

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 758 - 763

Published: Dec. 14, 2022

Language: Английский

Citations

670
SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development DOI Creative Commons
Danyi Ao,

Tianxia Lan,

Xuemei He

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

Abstract New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread the virus in ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), latest variant concern (VOC), has so far shown exceptional and infectivity established itself as dominant recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for recognition binding to host cell angiotensin‐converting enzyme receptors. harbors cluster substitutions/deletions/insertions, more than 30 mutations are located spike. Some noticeable mutations, including K417N, T478K, N501Y, P681H, shared with previous VOCs Alpha, Beta, Gamma, or Delta have been proven be associated higher transmissibility, viral infectivity, immune evasion potential. Studies revealed that partially resistant neutralizing activity therapeutic antibodies convalescent sera, which poses significant challenges clinical effectiveness current vaccines antibodies. We provide comprehensive analysis summary epidemiology escape mechanisms variant. also suggest some strategies against This review, therefore, aims information further research efforts prevent contain impact new during

Language: Английский

Citations

108
The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far DOI Creative Commons
Vivek P. Chavda, Rajashri Bezbaruah,

Kangkan Deka

et al.

Vaccines, Journal Year: 2022, Volume and Issue: 10(11), P. 1926 - 1926

Published: Nov. 14, 2022

The world has not yet completely overcome the fear of havoc brought by SARS-CoV-2. virus undergone several mutations since its initial appearance in China December 2019. Several variations (i.e., B.1.616.1 (Kappa variant), B.1.617.2 (Delta B.1.617.3, and BA.2.75 (Omicron variant)) have emerged throughout pandemic, altering virus's capacity to spread, risk profile, even symptoms. Humanity faces a serious threat as long keeps adapting changing fundamental function evade immune system. Delta variant two escape alterations, E484Q L452R, well other mutations; most notable these is P681R, which expected boost infectivity, whereas Omicron about 60 with certain deletions insertions. 40-60% more contagious comparison Alpha variant. Additionally, AY.1 lineage, also known "Delta plus" variant, surfaced result mutation was one causes life-threatening second wave coronavirus disease 2019 (COVID-19). Nevertheless, recent variants represent reminder that COVID-19 epidemic far from ending. sparked fervor investigation on why initially appeared propagate so much rapidly than three concerns (VOCs), whether it threatening those ways, how type mutations, induce minor changes proteins, can wreck trouble. This review sheds light pathogenicity, treatments, impact vaccine efficacy

Language: Английский

Citations

75
Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC) DOI Creative Commons
Sindhu Mohandas, Prasanna Jagannathan, Timothy J. Henrich

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 26, 2023

With a global tally of more than 500 million cases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses key determinants severity and outcomes initial well subsequent PASC. The complexity innate adaptive in period requires in-depth mechanistic analyses identify specific molecular signals cell populations which promote PASC pathogenesis. In this review, we examine current literature on mechanisms dysregulation COVID-19 limited emerging data immunopathology While phases may share some parallel immunopathology, it is likely quite distinct heterogeneous, thus requiring large-scale longitudinal patients with without after an infection. By outlining knowledge gaps PASC, hope provide avenues for novel research directions will ultimately lead precision therapies restore healthy function patients.

Language: Английский

Citations

63
Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue DOI Creative Commons

Guoli Shi,

Tiansheng Li, Kin Kui Lai

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 30, 2024

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue spread. Here, we show exhibits increased infectivity in primary adult upper airway tissue relative Delta. Using recombinant forms nasal epithelial cells cultured at the liquid-air interface, mutations unique Spike enable enhanced entry into tissue. Unlike earlier SARS-CoV-2, our findings suggest enters independently serine transmembrane proteases instead relies upon metalloproteinases catalyze membrane fusion. Furthermore, demonstrate this pathway unlocked by enables evasion from constitutive interferon-induced antiviral factors restrict attachment. Therefore, transmissibility exhibited humans may be attributed not only its vaccine-elicited adaptive immunity, but also superior invasion epithelia resistance cell-intrinsic barriers present therein.

Language: Английский

Citations

19
The role of SARS-CoV-2 accessory proteins in immune evasion DOI
Milad Zandi, Maryam Shafaati, Davood Kalantar-Neyestanaki

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113889 - 113889

Published: Oct. 17, 2022

Language: Английский

Citations

65
Unique mutations in SARS-CoV-2 Omicron subvariants' non-spike proteins: Potential impacts on viral pathogenesis and host immune evasion DOI
Anamica Hossain,

Shammi Akter,

Alfi Anjum Rashid

et al.

Microbial Pathogenesis, Journal Year: 2022, Volume and Issue: 170, P. 105699 - 105699

Published: Aug. 6, 2022

Language: Английский

Citations

64
SARS‐CoV‐2 NSP7 inhibits type I and III IFN production by targeting the RIG‐I/MDA5, TRIF, and STING signaling pathways DOI

Jian Deng,

Yi Zheng,

Shengnan Zheng

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(3)

Published: Feb. 9, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited production type I III interferons (IFNs) by targeting RIG-I/MDA5, Toll-like receptor (TLR3)-TRIF, cGAS-STING signaling pathways. suppressed expression IFNs IFN-stimulated genes induced poly (I:C) transfection infection with Sendai virus or virus-like particles. impaired IFN activated components cytosolic dsRNA-sensing pathway, including RIG-I, MDA5, MAVS, but not TBK1, IKKε, IRF3-5D, an active form IRF3. In addition, also TRIF- STING-induced responses. Mechanistically, associated RIG-I MDA5 prevented formation RIG-I/MDA5-MAVS signalosome interacted TRIF STING to inhibit TRIF-TBK1 STING-TBK1 complex formation, thus reducing subsequent IRF3 phosphorylation nuclear translocation are essential for induction. ectopic impeded immune activation facilitated replication. Taken together, dampens responses via disruption signal transduction RIG-I/MDA5-MAVS, TLR3-TRIF, pathways, providing novel insights into interactions between immunity.

Language: Английский

Citations

29
Efficacy of interferon alpha for the treatment of hospitalized patients with COVID-19: A meta-analysis DOI Creative Commons
Mykhailo Buchynskyi, Iryna Kamyshna,

Katerina Lyubomirskaya

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

Introduction IFN-α intervention may block SARS-CoV-2 replication and normalize the deregulated innate immunity of COVID-19. Aim This meta-analysis aimed to investigate efficacy interferon IFN-α–containing regimens when treating patients with moderate-to-severe Material methods PubMed, SCOPUS, ClinicalTrials.gov were searched from inception 15 January 2022. A systematic literature search was conducted by applying relevant terms for ‘COVID-19’ ‘interferon-α’. The primary outcome enclosed all-cause hospital mortality. secondary outcomes constituted length stay; discharge; nucleic acid negative conversion. Results Eleven studies are in meta-analysis. No significant difference mortality rate found between study control groups (OR 0.2; 95% CI 0.05-1.2; I 2 = 96%). implementation did not influence such as stay 0.9; CІ, 0.3-2.6; 91%), conversion 0.8; CI, 0.04-17.2; 94%). Nevertheless, treatment resulted a higher number discharged 26.6; 2.7-254.3; 95%). Conclusions Thus, does benefit survival hospitalized COVID-19 but increase hospital. Systematic review registration www.crd.york.ac.uk/prospero , identifier (CRD42022374589).

Language: Английский

Citations

27