tetano
Editor, Senior Moderator
Sci Rep
. 2024 Oct 28;14(1):25734.
doi: 10.1038/s41598-024-76401-1. SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains
Mariam Merchant[SUP] 1 [/SUP], Javaria Ashraf[SUP] 1 [/SUP], Kiran Iqbal Masood[SUP] 1 [/SUP], Maliha Yameen[SUP] 1 [/SUP], Rabia Hussain[SUP] 1 [/SUP], Asghar Nasir[SUP] 1 [/SUP], Zahra Hasan[SUP] 2 [/SUP]
Affiliations
SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.Comparison of transcriptional profiles of Symptomatic and Asymptomatic COVID-19 cases showed increased differentially regulated gene (DEGs) of inflammatory, apoptosis and blood coagulation pathways, with decreased T cell and Interferon stimulated genes (ISG) activation. Between SARS-CoV-2 strains, an increasing number of DEGs occurred in comparisons between wt and alpha (196), delta (1425) or, omicron (2313) infections. COVID-19 cases with alpha or, delta variants demonstrated suppression transcripts of innate immune pathways. EGR1 and CXCL8 were highly upregulated in those infected with VOC; heme biosynthetic pathway genes (ALAS2, HBB, HBG1, HBD9) and ISGs were downregulated. Delta and omicron infections upregulated ribosomal pathways, reflecting increased viral RNA translation. Asymptomatic COVID-19 cases infected with delta infections showed increased cytokines and ISGs expression. Overall, increased inflammation, with reduced host heme synthesis was associated with infections caused by VOC infections, with raised type I interferon in cases with less severe disease.
Keywords: ALAS2; Delta variant; EGR1; ISG; SARS-CoV-2; Variants of concern.
. 2024 Oct 28;14(1):25734.
doi: 10.1038/s41598-024-76401-1. SARS-CoV-2 variants induce increased inflammatory gene expression but reduced interferon responses and heme synthesis as compared with wild type strains
Mariam Merchant[SUP] 1 [/SUP], Javaria Ashraf[SUP] 1 [/SUP], Kiran Iqbal Masood[SUP] 1 [/SUP], Maliha Yameen[SUP] 1 [/SUP], Rabia Hussain[SUP] 1 [/SUP], Asghar Nasir[SUP] 1 [/SUP], Zahra Hasan[SUP] 2 [/SUP]
Affiliations
- PMID: 39468120
- PMCID: PMC11519399
- DOI: 10.1038/s41598-024-76401-1
SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.Comparison of transcriptional profiles of Symptomatic and Asymptomatic COVID-19 cases showed increased differentially regulated gene (DEGs) of inflammatory, apoptosis and blood coagulation pathways, with decreased T cell and Interferon stimulated genes (ISG) activation. Between SARS-CoV-2 strains, an increasing number of DEGs occurred in comparisons between wt and alpha (196), delta (1425) or, omicron (2313) infections. COVID-19 cases with alpha or, delta variants demonstrated suppression transcripts of innate immune pathways. EGR1 and CXCL8 were highly upregulated in those infected with VOC; heme biosynthetic pathway genes (ALAS2, HBB, HBG1, HBD9) and ISGs were downregulated. Delta and omicron infections upregulated ribosomal pathways, reflecting increased viral RNA translation. Asymptomatic COVID-19 cases infected with delta infections showed increased cytokines and ISGs expression. Overall, increased inflammation, with reduced host heme synthesis was associated with infections caused by VOC infections, with raised type I interferon in cases with less severe disease.
Keywords: ALAS2; Delta variant; EGR1; ISG; SARS-CoV-2; Variants of concern.