Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 46(1), P. 75 - 90

Published: Nov. 16, 2022

Language: Английский

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Interferon- γ and infectious diseases: Lessons and prospects

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these would benefit not just new medicines vaccines but also a better understanding what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as macrophage-activating factor, and, in recent years, there has been resurgent interest biology its role human defense. Here we assess current IFN-γ, revisit designation an "interferon," weigh prospects therapeutic globally pervasive microbial pathogens.

Language: Английский

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Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-Analysis

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 430 - 430

Published: Jan. 28, 2023

The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review meta-analysis provide information regarding regional differences in as well an estimate global based on 62 studies reporting 626,035 patients infected with variant. omicron-induced European ancestry 11.7%, while it significantly lower all other populations, ranging 1.9% 4.9%. When ethnic population sizes are considered, adults estimated be 3.7%. Omicron's effect olfaction twofold tenfold that alpha or delta according meta-analyses our analysis directly compared variants. profile ethnicities mirrors results a recent genome-wide association study connected gene locus encoding odorant-metabolizing enzyme, UDP glycosyltransferase, extent COVID-19-related loss smell. consistent hypothesis this enzyme contributes observed differences.

Language: Английский

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

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

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Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Cross-species transmission of animal viruses poses a threat to human health. However, systematic experimental assessments these risks remain scarce. A critical step in viral infection is cellular internalization mediated by receptor-binding proteins (RBPs). Here we constructed pseudotypes bearing the RBPs 102 enveloped RNA and assayed their infectivity across 5,202 RBP–cell combinations. This showed that most tested have potential enter cells. Pseudotype varied widely among 14 families examined was influenced RBP characteristics, host origin target cell type. Cellular gene expression data revealed availability specific cell-surface receptors not necessarily main factor limiting entry additional factors must be considered. Altogether, results suggest weak interspecies barriers early stages advance our understanding molecular interactions driving zoonosis.

Language: Английский

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PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection

Nature, Journal Year: 2023, Volume and Issue: 619(7971), P. 819 - 827

Published: July 12, 2023

Abstract Understanding protective immunity to COVID-19 facilitates preparedness for future pandemics and combats new SARS-CoV-2 variants emerging in the human population. Neutralizing antibodies have been widely studied; however, on basis of large-scale exome sequencing protected versus severely ill patients with COVID-19, local cell-autonomous defence is also crucial 1–4 . Here we identify phospholipid scramblase 1 (PLSCR1) as a potent restriction factor against live infection parallel genome-wide CRISPR–Cas9 screens lung epithelia hepatocytes before after stimulation interferon-γ (IFNγ). IFNγ-induced PLSCR1 not only restricted USA-WA1/2020, but was effective Delta B.1.617.2 Omicron BA.1 lineages. Its robust activity extended other highly pathogenic coronaviruses, functionally conserved bats mice, interfered uptake both endocytic TMPRSS2-dependent fusion routes. Whole-cell 4Pi single-molecule switching nanoscopy together bipartite nano-reporter assays found that directly targeted SARS-CoV-2-containing vesicles prevent spike-mediated viral escape. A C-terminal β-barrel domain—but lipid activity—was essential this fusogenic blockade. Our mechanistic studies, reports COVID-associated mutations are some susceptible people 3,4 , an anti-coronavirus protein interferes at late entry step RNA released into host-cell cytosol.

Language: Английский

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Viral Membrane Fusion: A Dance Between Proteins and Lipids

Annual Review of Virology, Journal Year: 2023, Volume and Issue: 10(1), P. 139 - 161

Published: Sept. 29, 2023

There are at least 21 families of enveloped viruses that infect mammals, and many contain members high concern for global human health. All have a dedicated fusion protein or complex enacts the critical genome-releasing membrane event is essential before viral replication within host cell interior can begin. Because all enter cells by fusion, it behooves us to know how proteins function. Viral also major targets neutralizing antibodies, hence they serve as key vaccine immunogens. Here we review current concepts about focusing on triggered, structural intermediates between pre- postfusion forms, their interplay with lipid bilayers engage. We discuss cellular therapeutic interventions thwart virus-cell fusion.

Language: Английский

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Interferon‐induced transmembrane protein 3 (IFITM3) limits lethality of SARS‐CoV‐2 in mice

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(4)

Published: March 7, 2023

Abstract Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral that alters cell membranes to block fusion of viruses. Conflicting reports identified opposing effects IFITM3 on SARS‐CoV‐2 infection cells, and its impact viral pathogenesis in vivo remains unclear. Here, we show knockout (KO) mice infected with experience extreme weight loss lethality compared mild wild‐type (WT) mice. KO have higher lung titers increases inflammatory cytokine levels, immune infiltration, histopathology. Mechanistically, observe disseminated antigen staining throughout the pulmonary vasculature mice, as well increased heart infection, indicating constrains dissemination SARS‐CoV‐2. Global transcriptomic analysis lungs shows upregulation gene signatures associated interferons, inflammation, angiogenesis versus WT animals, highlighting changes expression programs precede severe pathology fatality. Our results establish a new animal model for studying overall demonstrate protective infections .

Language: Английский

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Host cell-intrinsic innate immune recognition of SARS-CoV-2

Current Opinion in Virology, Journal Year: 2021, Volume and Issue: 52, P. 30 - 38

Published: Nov. 11, 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged at the end of 2019 and caused pandemic coronavirus disease (COVID-19). Basic clinical investigations indicate that severe forms COVID-19 are due in part to dysregulated immune responses virus infection. The innate system is first line host defense against most infections, with pathogen recognition receptors detecting SARS-CoV-2 RNA protein components initiating pro-inflammatory antiviral responses. Notwithstanding this response, proteins evade, inhibit, skew signaling early In review, we highlight cell-based infection mechanisms employed by modulate these pathways.

Language: Английский

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IFITM protein regulation and functions: Far beyond the fight against viruses

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 18, 2022

Interferons (IFNs) are important cytokines that regulate immune responses through the activation of hundreds genes, including interferon-induced transmembrane proteins (IFITMs). This evolutionarily conserved protein family includes five functionally active homologs in humans. Despite high sequence homology, IFITMs vary expression, subcellular localization and function. The initially described adhesive antiproliferative or pro-oncogenic functions IFITM were diluted by discovery their antiviral properties. large set viruses is inhibited these constantly expanding, as possible mechanisms action. In addition to beneficial effects, often upregulated a broad spectrum cancers. have been linked most hallmarks cancer, tumor cell proliferation, therapeutic resistance, angiogenesis, invasion, metastasis. Recent studies involvement antitumor immunity. review summarizes various levels regulation physiological pathological proteins, with an emphasis on tumorigenesis

Language: Английский

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