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. 2023 Aug 24;24(17):13146.
doi: 10.3390/ijms241713146.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants

Guilherme C da Fonseca  1 , Liliane T F Cavalcante  1 , Otávio J Brustolini  1 , Paula M Luz  2 , Debora C Pires  2 , Emilia M Jalil  2 , Eduardo M Peixoto  2 , Beatriz Grinsztejn  2 , Valdilea G Veloso  2 , Sandro Nazer  2 , Carlos A M Costa  3 , Daniel A M Villela  4 , Guilherme T Goedert  5 , Cleber V B D Santos  6 , Nadia C P Rodrigues  3   6 , Fernando do Couto Motta  7 , Marilda Mendonça Siqueira  7 , Lara E Coelho  2 , Claudio J Struchiner  5   7 , Ana Tereza R Vasconcelos  1
Affiliations

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants

Guilherme C da Fonseca et al. Int J Mol Sci. .

Abstract

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Keywords: Delta; Gamma; SARS-CoV-2 variants; innate immune system; type-I interferon response; viral evolution.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dot blot of Gene Ontology (GO) enrichment of all differentially expressed genes (DEGs): (A) Gamma group; (B) Delta group.
Figure 2
Figure 2
Venn diagrams: (A) upregulated and (B) downregulated shared and exclusively DEGs between Gamma and Delta transcriptomes. Only results for FDR p < 0.05 are displayed.
Figure 3
Figure 3
Reactome enrichment cnetplot of exclusively upregulated DEGs of Delta-infected group.
Figure 4
Figure 4
Gamma interactome of the top 20 most connected differentially expressed genes (DEGs), defense response to virus genes, angiogenesis genes, adaptive and innate immune genes, and SARS-CoV-2 proteins. Genes with a purple star are genes that are part of the SARS-CoV-2 disease pathway and are found in Delta and Gamma DEGs.
Figure 5
Figure 5
Delta interactome of the top 20 most connected differentially expressed genes (DEGs), defense response to virus genes, angiogenesis genes, adaptive and innate immune genes, and SARS-CoV-2 proteins. Genes with a purple star are genes that are part of the SARS-CoV-2 disease pathway and are found in Delta and Gamma DEGs. Genes with a yellow star are genes that are part of the SARS-CoV-2 disease pathway and are found only in Delta DEGs.
Figure 6
Figure 6
Type-I interferon response triggered by Delta and Gamma. On the left is a schematic showing the genes differentially expressed in the transcriptome of individuals infected with the Delta variant and the interaction with viral proteins and mutations that affect the interferon response. On the right is the same scheme with the transcriptome of people infected with Gamma. PRRs—pattern recognition receptors. Created with biorender.com (accessed on 7 July 2023).
See this image and copyright information in PMC

References

    1. Li W., Wang H., Zheng S.J. Roles of RNA Sensors in Host Innate Response to Influenza Virus and Coronavirus Infections. Int. J. Mol. Sci. 2022;23:8285. doi: 10.3390/ijms23158285. - DOI - PMC - PubMed
    1. Chiang C., Gack M.U. Post-translational Control of Intracellular Pathogen Sensing Pathways. Trends Immunol. 2016;38:39–52. doi: 10.1016/j.it.2016.10.008. - DOI - PMC - PubMed
    1. Al-Rohaimi A.H., Al Otaibi F. Novel SARS-CoV-2 outbreak and COVID-19 disease; a systemic review on the global pandemic. Genes Dis. 2020;7:491–501. doi: 10.1016/j.gendis.2020.06.004. - DOI - PMC - PubMed
    1. Anderson R.M., Fraser C., Ghani A.C., Donnelly C.A., Riley S., Ferguson N.M., Leung G.M., Lam T.H., Hedley A.J. Epidemiology, transmission dynamics and control of SARS: The 2002–2003 epidemic. Philos. Trans. R. Soc. B Biol. Sci. 2004;359:1091–1105. doi: 10.1098/rstb.2004.1490. - DOI - PMC - PubMed
    1. Arden K.E., Nissen M.D., Sloots T.P., Mackay I.M. New human coronavirus, HCoV-NL63, associated with severe lower respiratory tract disease in Australia. J. Med. Virol. 2005;75:455–462. doi: 10.1002/jmv.20288. - DOI - PMC - PubMed

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