Differential type I interferon response in buffy coat transcriptome of individuals infected with SARS-CoV-2 Gamma and Delta variants

The innate immune system is the first line of defence against pathogens as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I interferon (IFN) response activation at the initial steps of infection is essential to prevent viral replication and tissue damage. Both SARS-CoV and SARS-CoV-2 are able to inhibit this activation and patients who have a dysregulated IFN-I response are more likely to developed a more severe disease. Several mutations in different varaints of SARS-CoV-2 have been showed potential to interfere in the immune system. Here we evaluate the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome present more genes enriched to innate immune response and the Gamma to adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the type I IFN response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein that were found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicate that the Gamma variant evolve to evade the type I IFN response. In this work it was shown one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.