The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling

Journal of General Virology, Journal Year: 2014, Volume and Issue: 95(4), P. 874 - 882

Published: Jan. 18, 2014

The recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV), a betacoronavirus, is associated with severe pneumonia and renal failure. environmental origin of MERS-CoV as yet unknown; however, its genome sequence closely related to those two bat coronaviruses, named BtCoV-HKU4 BtCoV-HKU5, which were derived from Chinese samples. A hallmark highly pathogenic viruses their ability evade the innate immune response host. CoV accessory proteins, for example acute (SARS-CoV), have been shown block antiviral signalling pathways. MERS-CoV, similar SARS-CoV, has inhibit type I IFN induction in variety cell types vitro. We therefore hypothesized that phylogenetically BtCoV-HKU5 may encode proteins capabilities. In this study, we demonstrated ORF4b-encoded protein (p4b) indeed facilitate evasion by inhibiting NF-κB also analysed subcellular localization p4b all are localized nucleus.

Language: Английский

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Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses

mBio, Journal Year: 2020, Volume and Issue: 11(3)

Published: June 1, 2020

The ongoing COVID-19 pandemic strongly emphasizes the need for a more complete understanding of biology and pathogenesis its causative agent SARS-CoV-2. Despite intense scrutiny, several proteins encoded by genomes SARS-CoV-2 other SARS-like coronaviruses remain enigmatic. Moreover, high infectivity severity in certain individuals make wet-lab studies currently challenging. In this study, we used series computational strategies to identify fast-evolving regions which are potentially under host immune pressure. Most notably, hitherto-uncharacterized protein ORF8 is one them. Using sensitive sequence structural analysis methods, show that from alpha- beta-coronavirus comprise novel families immunoglobulin domain proteins, might function as potential modulators delay or attenuate response against viruses.

Language: Английский

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Crosstalk between the Type 1 Interferon and Nuclear Factor Kappa B Pathways Confers Resistance to a Lethal Virus Infection

Cell Host & Microbe, Journal Year: 2013, Volume and Issue: 13(6), P. 701 - 710

Published: June 1, 2013

Language: Английский

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Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 78(4), P. 1423 - 1444

Published: Oct. 21, 2020

Language: Английский

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Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection

Immunity, Journal Year: 2015, Volume and Issue: 43(6), P. 1148 - 1159

Published: Dec. 1, 2015

Language: Английский

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Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection

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

Published: April 16, 2024

Abstract The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation vaccination campaign against virus. Consequently, immunity and related orthopoxviruses like Monkeypox virus gradually declines, highlighting need for efficient countermeasures not only prevention, but also treatment already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 EV42, targeting two infectious forms virus, were selected vivo evaluation, based on their vitro neutralization potency. A single dose either or EV42 administered three days post-infection (dpi) BALB/c female mice provides full protection lethal ectromelia challenge. Importantly, a combination both mAbs confers even when provided five dpi. Whole-body bioimaging viral load analysis reveal that allows faster more clearance target organs compared separately. combined further post-exposure currently circulating Cast/EiJ mice, therapeutic potential other orthopoxviruses.

Language: Английский

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Innate and adaptive immune responses that control lymph-borne viruses in the draining lymph node

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(9), P. 999 - 1007

Published: June 25, 2024

Abstract The interstitial fluids in tissues are constantly drained into the lymph nodes (LNs) as through afferent lymphatic vessels and from LNs blood efferent lymphatics. strategically positioned have appropriate cellular composition to serve sites of adaptive immune initiation against invading pathogens. However, for lymph-borne viruses, which disseminate entry site other system, cells draining LN (dLN) also play critical roles curbing systemic viral dissemination during primary secondary infections. Lymph-borne viruses can be transported dLNs free virions or within infected cells. Regardless mechanism, myeloid antigen-presenting cells, including various subtypes dendritic inflammatory monocytes, macrophages, a role initiating innate response dLN. This involves crosstalk between bystander that ultimately produce type I interferons (IFN-Is) cytokines recruit monocytes natural killer (NK) IFN-I NK cell cytotoxicity restrict spread infections prevent serious disease. Additionally, memory CD8 + T-cells reside rapidly migrate dLN contribute disease prevention review explores intricate responses orchestrated contain following infection T-cell vaccination.

Language: Английский

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The Pathogenesis and Immunobiology of Mousepox

Advances in immunology, Journal Year: 2015, Volume and Issue: unknown, P. 251 - 276

Published: Nov. 22, 2015

Language: Английский

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A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Dec. 17, 2018

Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted interact glycosaminoglycans expressed at the cell surface, but biological significance of this activity in vivo is poorly understood. Here, we show type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires to confer full virulence these retain immunomodulatory activity. Expression a variant form IFNα/βBP that inhibits IFN activity, does not surface glycosaminoglycans, results highly attenuated similar deletion mutant viruses. Transcriptomics analysis infection receptor-deficient mice confirmed control main function vivo. We propose retention may largely enhance their

Language: Английский

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Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node

Cell Reports, Journal Year: 2018, Volume and Issue: 24(1), P. 142 - 154

Published: July 1, 2018

Circulating natural killer (NK) cells help protect the host from lympho-hematogenous acute viral diseases by rapidly entering draining lymph nodes (dLNs) to curb virus dissemination. Here, we identify a highly choreographed mechanism underlying this process. Using footpad infection with ectromelia virus, pathogenic DNA of mice, show that TLR9/MyD88 sensing induces NKG2D ligands in virus-infected, skin-derived migratory dendritic (mDCs) induce production IFN-γ classical NK and other types group 1 innate lymphoid (ILCs) already dLNs, via NKG2D. Uninfected inflammatory monocytes, also recruited dLNs mDCs TLR9/MyD88-dependent manner, respond secreting CXCL9 for optimal CXCR3-dependent recruitment circulating cells. This work unveils whereby three cell types—mDCs, ILCs (mostly cells), monocytes—coordinate protective dLNs.

Language: Английский

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