The Evolutionary Dance between Innate Host Antiviral Pathways and SARS-CoV-2

Aliyari, Saba R.; Quanquin, Natalie; Pernet, Olivier; Zhang, Shilei; Wang, Lulan; Cheng, Genhong

doi:10.3390/pathogens11050538

Cited by 6 publications

(4 citation statements)

References 241 publications

(309 reference statements)

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“…Furthermore, besides mutations in the spike sequence in the SARS-CoV-2 variants genome, additional mutations may be present in other regions of the viral genome, including deletions in the ORF7a and ORF7b sequences (Jelley et al ., 2022; Mazur-Panasiuk et al ., 2021; Panzera et al ., 2021; Pyke et al ., 2021). ORF7a and ORF7b have been related to viral-induced apoptosis, and to interference with the innate immunity and the antiviral response (Aliyari et al, 2022; Hayn et al, 2021; Schaecher et al, 2007; Su et al, 2021), without, however, being essential to viral infection and replication (Schaecher et al, 2008; Silvas et al, 2021). Further, ORF7b has the potential to interfere with cell adhesion proteins in the olfactory mucosa (Fogeron et al ., 2021), and interestingly, a binary interaction between ORF7b and the human olfactory receptor OR1D5 has also been reported (Kim et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

Melo

Perraud

Alvarez

et al. 2022

Preprint

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Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Several studies have focused on the neuropathogenesis of the original SARS-CoV-2, but little is known about the neuropathological potential of the variants. Here, we assessed the clinical, olfactory and inflammatory conditions of golden hamsters infected with the original SARS-CoV-2, its ORF7-deleted mutant, and three variants: Gamma, Delta and Omicron/BA.1. We show that infected animals developed a variant-dependent clinical disease, and that the ORF7 of SARS-CoV-2 contribute to causing olfactory disturbances. Conversely, all SARS-CoV-2 variants were found to be neuroinvasive, regardless of the clinical presentation they induce. With newly-generated nanoluciferase-expressing SARS-CoV-2, we validated the olfactory pathway as a main entry point towards the brain, confirming that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

Melo

Perraud

Alvarez

et al. 2022

Preprint

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“…Then, the virus may be delivering their content to early endosomes via CCV. These mechanisms could be expressing in Sars-CoV-2 using different ways as by lysing the host cell, blocking the host innate defenses via IKBKE/IKK-epsilon kinase inhibition, JAK1 protein, DDX58/RIG-I-like repector (RLR) what stabilises the antiviral state, TBK1 kinase inhibition to prevent IRF activation, or toll-like recognition receptor (TLR) pathway evasion, which makes the production of interferons to be inhibited and so to establish a stable antiviral state ( Chen et al, 2021 ; Aliyari et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma proteome dynamics of COVID-19 severity learnt by a graph convolutional network of multi-scale topology

2023

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Efforts to understand the molecular mechanisms of COVID-19 have led to the identification of ACE2 as the main receptor for the SARS-CoV-2 spike protein on cell surfaces. However, there are still important questions about the role of other proteins in disease progression. To address these questions, we modelled the plasma proteome of 384 COVID-19 patients using protein level measurements taken at three different times and incorporating comprehensive clinical evaluation data collected 28 d after hospitalisation. Our analysis can accurately assess the severity of the illness using a metric based on WHO scores. By using topological vectorisation, we identified proteins that vary most in expression based on disease severity, and then utilised these findings to construct a graph convolutional network. This dynamic model allows us to learn the molecular interactions between these proteins, providing a tool to determine the severity of a COVID-19 infection at an early stage and identify potential pharmacological treatments by studying the dynamic interactions between the most relevant proteins.

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“…The prevalence of anosmia is higher in mild rather than moderate-to-critical COVID-19 forms [28]. The accessory protein ORF7 of SARS-CoV-2, which has been shown to interact with ORs [82], cell adhesion proteins in the olfactory mucosa [83] as well as components of the host's innate immunity [84][85][86], possibly contributes to the prolongation of OD [87].…”

Section: Viral Factors Contributing To Covid-19-related Loss Of Smellmentioning

confidence: 99%

The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID

Anastassopoulou,

Davaris,

Ferous

et al. 2024

Lifestyle Genomics

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Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.

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The Evolutionary Dance between Innate Host Antiviral Pathways and SARS-CoV-2

Cited by 6 publications

References 241 publications

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

Plasma proteome dynamics of COVID-19 severity learnt by a graph convolutional network of multi-scale topology

The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID

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