Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population

Moura, Ronald; Agrelli, Almerinda; Santos-Silva, Carlos André dos; Silva, Natália; Assunção, Bruno Rodrigo; Brandão, Lucas; Benko‐Iseppon, Ana Maria; Crovella, Sérgio

doi:10.1136/jclinpath-2020-206946

Cited by 14 publications

(18 citation statements)

References 26 publications

(31 reference statements)

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“…HLA-C is another example of a candidate for mediating COVID-19 severity since specific HLA subtypes have been associated with susceptibility for many viral infections, including HIV, HBV, H1N1, HCV and HPV [36] . From a functional standpoint, HLA-C is involved in both innate and adaptive immunity, but most importantly, HLA-C haplotypes have also been linked to the clinical course of COVID-19 [37] , [38] , [39] , [40] .…”

Section: Resultsmentioning

confidence: 99%

“…However, as also occurred with AIM2, the overactivation of HLA-C can cause autoimmune reactions and the excessive release of cytokines leading to an exacerbated immune response. In this regard, HLA-C genetic variants are known to be associated with COVID-19 clinical outcome [37] , [38] , [39] , [40] . Importantly for the natural history of COVID-19 infection, GWAS have also shown that HLA-C constitutes a susceptibility locus for human pneumonia [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

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Epigenome-wide association study of COVID-19 severity with respiratory failure

et al. 2021

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Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery ( n = 207) and validation ( n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. Funding The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epigenome-wide association study of COVID-19 severity with respiratory failure

et al. 2021

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“…Although immunogenic epitopes in both the structural and non-structural proteins of SARS-CoV-2 that could interact with the MHC-I alleles were identified [ 128 , 129 ], the role of immunoproteasome in SARS-CoV-2 infection specifically remains to be investigated. While it might be seminal to elicit an anti-viral adaptive response in the site of infection, it is likely that during the late phases of infection, when a cytokine storm takes place, the immunoproteasome might be strongly and persistently recruited to promote an excessive immune reaction fueling autophagy impairment.…”

Section: What We Know Do Not Know and What We Can Hypothesize Onmentioning

confidence: 99%

Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis

et al. 2020

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The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), other features became evident in the context of COVID-19. These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations. The multi-system nature of such viral infection is a witness to the exploitation and impairment of ubiquitous subcellular and metabolic pathways for the sake of its life-cycle, ranging from host cell invasion, replication, transmission, up to a cytopathic effect and overt systemic inflammation. In this frame, alterations in cell-clearing systems of the host are emerging as a hallmark in the pathogenesis of various respiratory viruses, including SARS-CoV-2. Indeed, exploitation of the autophagy and proteasome pathways might contribute not only to the replication of the virus at the site of infection but also to the spreading of either mature virions or inflammatory mediators at both cellular and multisystem levels. In this frame, besides a pharmacological therapy, many researchers are wondering if some non-pharmacological substances might counteract or positively modulate the course of the infection. The pharmacological properties of natural compounds have gained increasing attention in the field of alternative and adjunct therapeutic approaches to several diseases. In particular, several naturally-occurring herbal compounds (mostly polyphenols) are reported to produce widespread antiviral, anti-inflammatory, and anti-oxidant effects while acting as autophagy and (immuno)-proteasome modulators. This article attempts to bridge the perturbation of autophagy and proteasome pathways with the potentially beneficial effects of specific phytochemicals and flavonoids in viral infections, with a focus on the multisystem SARS-CoV-2 infection.

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“… [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] ...…”

Section: Uncited Referencesunclassified

Antigen presentation in SARS-CoV-2 infection: the role of class I HLA and ERAP polymorphisms

Saulle¹,

Vicentini²,

Clerici³

et al. 2021

Human Immunology

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Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent responsible for the recent COVID-19 pandemic. Several correlations have already been established between the expression of a specific HLA allele/haplotype and susceptibility/progression of SARS-CoV-2 infection and new ones are continuously emerging. Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the huge amount of existing variants, the data gathered in such a brief span of time are to some extent confusing and contradictory. The aim of this mini-review is to provide a snap-shot of the main findings so far collected on the HLA-SARS-CoV-2 interaction, so as to partially untangle this intricate yarn. As key factors in the generation of antigenic peptides to be presented by HLA molecules, ERAP1 and ERAP2 role in SARS-CoV-2 infection will be revised as well.

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Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population

Cited by 14 publications

References 26 publications

Epigenome-wide association study of COVID-19 severity with respiratory failure

Epigenome-wide association study of COVID-19 severity with respiratory failure

Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis

Antigen presentation in SARS-CoV-2 infection: the role of class I HLA and ERAP polymorphisms

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