SARS-CoV-2 structural proteins affect the expression of IL-8 and TNF-α cytokines and APOBEC genes in human lung A549 and liver Huh-7 cells

The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of cytidine deami nases responsible for DNA and RNA sequence editing, playing pivotal roles in a wide range of biological processes, including immune responses, antiviral properties, and genetic mutations. In this work, we investigated the effect of SARS-CoV-2 structural proteins – Envelope (E), Spike (S), Nucleocapsid (N), Membrane (M) and protein ORF6 – on the expression of cytokines Interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α), and APOBEC3s proteins (APOBEC3B and APOBEC3F) genes in Huh-7 and A549 human cell lines. While there is plenty of scientific evidence about the effects of SARS-CoV-2 on the inflammatory cascade, the current literature regarding the impact of SARS-CoV-2 on APOBEC expression is scarce. Our findings reveal a complex relationship between SARS-CoV-2 structural proteins and the host immune response, as certain viral structural proteins (S, M, E) modulate cytokine expression, potentially contributing to the dysregulated immune responses seen in COVID-19 patients. Additionally, our research uncovered interactions between viral proteins and APOBEC genes. This study contributes to a better understanding of the host-virus interactions in the context of SARS-CoV-2 infection and provides some insights into potential therapeutic targets for mitigating the immunopathological consequences of the disease.