Dataset Information

Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature.

ABSTRACT: Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1? and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1? and IL-6 in severe cases can improve patient outcome.

SUBMITTER: Schoeman D

PROVIDER: S-EPMC7496634 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature.

Schoeman Dewald D Fielding Burtram C BC

Frontiers in microbiology 20200903

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show ...[more]

PMID: 33013759

Similar Datasets

Project description:Feline coronaviruses (FCoVs) commonly cause mild enteric infections in felines worldwide (termed feline enteric coronavirus [FECV]), with around 12 per cent developing into deadly feline infectious peritonitis (FIP; feline infectious peritonitis virus [FIPV]). Genomic differences between FECV and FIPV have been reported, yet the putative genotypic basis of the highly pathogenic phenotype remains unclear. Here, we used state-of-the-art molecular evolutionary genetic statistical techniques to identify and compare differences in natural selection pressure between FECV and FIPV sequences, as well as to identify FIPV- and FECV-specific signals of positive selection. We analyzed full-length FCoV protein coding genes thought to contain mutations associated with FIPV (Spike, ORF3abc, and ORF7ab). We identified two sites exhibiting differences in natural selection pressure between FECV and FIPV: one within the S1/S2 furin cleavage site (FCS) and the other within the fusion domain of Spike. We also found fifteen sites subject to positive selection associated with FIPV within Spike, eleven of which have not previously been suggested as possibly relevant to FIP development. These sites fall within Spike protein subdomains that participate in host cell receptor interaction, immune evasion, tropism shifts, host cellular entry, and viral escape. There were fourteen sites (twelve novel sites) within Spike under positive selection associated with the FECV phenotype, almost exclusively within the S1/S2 FCS and adjacent to C domain, along with a signal of relaxed selection in FIPV relative to FECV, suggesting that furin cleavage functionality may not be needed for FIPV. Positive selection inferred in ORF7b was associated with the FECV phenotype and included twenty-four positively selected sites, while ORF7b had signals of relaxed selection in FIPV. We found evidence of positive selection in ORF3c in FCoV-wide analyses, but no specific association with the FIPV or FECV phenotype. We hypothesize that some combination of mutations in FECV may contribute to FIP development, and that it is unlikely to be one singular 'switch' mutational event. This work expands our understanding of the complexities of FIP development and provides insights into how evolutionary forces may alter pathogenesis in coronavirus genomes.

Project description:BACKGROUND:The recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work has been conducted on other coronaviruses that affect different species. OBJECTIVES:We aimed to review the literature on host genetic factors related to coronaviruses, with a systematic focus on human studies. METHODS:We conducted a PubMed-based search and analysis for articles relevant to host genetic factors in coronavirus. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses. RESULTS:We identified 1,187 articles of potential relevance. Forty-five studies were related to human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small number of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, 174 involved study of non-human (animal) host genetic factors related to coronavirus, 584 involved study of non-genetic host factors related to coronavirus, including involving immunopathogenesis, 16 involved study of other pathogens (not coronavirus), 321 involved other studies of coronavirus, and 18 studies were assigned to the other categories and removed. KEY FINDINGS:We have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies to date have been limited by issues that may be less impactful on current endeavors, including relatively low numbers of eligible participants and limited availability of advanced genomic methods.

Dataset Information

Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature.

Publications

Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets