Continuous surveillance and detailed immunological profiling remain essential in adapting public health responses to the evolving landscape of SARS-CoV-2 variants. This study explores the differential ability of SARS-CoV-2 variants of concern (VOCs), evolved from the original Wuhan strain to the post-Omicron era, to elicit anti-viral and inflammatory responses by exploiting a human peripheral blood mononuclear cells (PBMCs)-based in vitro model. By using real-time RT-PCR analyses and multiplex cytokine-bead arrays, we observed that various SARS-CoV-2 VOCs induce unique antiviral gene signatures and distinct cytokine and chemokine profiles 24 hours post-stimulation. Specifically, we noted substantial variability in the levels of antiviral type I Interferon (IFN) production or transcription of the IFN-induced Mx dynamin-like GTPase I (Mx1) gene, as well as of the release of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), tumor necrosis factor a (TNF-a), C-C motif chemokine ligand 2 (CCL-2 or MCP-1) and CCL-5 (or Rantes), depending on the VOCs used to stimulate PBMC. These findings correlate with a different viral subgenomic RNA (sgRNAs) profile. Our study confirmed, indeed, that PBMCs do not support productive replication of SARS-CoV-2 in vitro; nonetheless, VOC-specific qualitative and quantitative differences in the detection of sgRNAs were found. While this result highlights a non-productive infection state in PBMCs, the presence of various sgRNAs can still modulate the immune response, potentially influencing antiviral signaling pathways and cytokine release. Characterization is also ongoing on the ability of VOCs to regulate intracellular redox-modulated pathways. By comparing the impact of different VOCs on cytokine production and sgRNA profiles in human immune cells, this research provides critical insights into the immune responses triggered by various SARS-CoV-2 variants, contributing to a better understanding of their pathogenicity and potential impact on disease severity and, thus, guiding the development of targeted therapeutic approaches.
Differential cytokine profile in SARS-CoV-2 VOCs-treated PBMCs: insights into viral subgenomic RNAs / Criscuolo, Elena; Severa, Martina; Castelli, Matteo; Cairo, Giada; Paola Etna, Marilena; Ricci, Daniela; DE ANGELIS, Marta; Nencioni, Lucia; Palamara, ANNA TERESA; Burioni, Roberto; Coccia, Eliana M.; Clementi, Nicola. - (2024). (Intervento presentato al convegno INF-ACT Meeting 2024 tenutosi a pavia, italia).
Differential cytokine profile in SARS-CoV-2 VOCs-treated PBMCs: insights into viral subgenomic RNAs
Matteo Castelli;Giada Cairo;Daniela Ricci;Marta De Angelis;Lucia Nencioni;Anna Teresa Palamara;
2024
Abstract
Continuous surveillance and detailed immunological profiling remain essential in adapting public health responses to the evolving landscape of SARS-CoV-2 variants. This study explores the differential ability of SARS-CoV-2 variants of concern (VOCs), evolved from the original Wuhan strain to the post-Omicron era, to elicit anti-viral and inflammatory responses by exploiting a human peripheral blood mononuclear cells (PBMCs)-based in vitro model. By using real-time RT-PCR analyses and multiplex cytokine-bead arrays, we observed that various SARS-CoV-2 VOCs induce unique antiviral gene signatures and distinct cytokine and chemokine profiles 24 hours post-stimulation. Specifically, we noted substantial variability in the levels of antiviral type I Interferon (IFN) production or transcription of the IFN-induced Mx dynamin-like GTPase I (Mx1) gene, as well as of the release of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), tumor necrosis factor a (TNF-a), C-C motif chemokine ligand 2 (CCL-2 or MCP-1) and CCL-5 (or Rantes), depending on the VOCs used to stimulate PBMC. These findings correlate with a different viral subgenomic RNA (sgRNAs) profile. Our study confirmed, indeed, that PBMCs do not support productive replication of SARS-CoV-2 in vitro; nonetheless, VOC-specific qualitative and quantitative differences in the detection of sgRNAs were found. While this result highlights a non-productive infection state in PBMCs, the presence of various sgRNAs can still modulate the immune response, potentially influencing antiviral signaling pathways and cytokine release. Characterization is also ongoing on the ability of VOCs to regulate intracellular redox-modulated pathways. By comparing the impact of different VOCs on cytokine production and sgRNA profiles in human immune cells, this research provides critical insights into the immune responses triggered by various SARS-CoV-2 variants, contributing to a better understanding of their pathogenicity and potential impact on disease severity and, thus, guiding the development of targeted therapeutic approaches.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
