In a recent study published in Nature Microbiology, researchers compared the replication of the concerning Omicron variant (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cell lines and primary airway cultures, measuring the host’s response to infection.
The evolution of SARS-CoV-2 has led to the development of VOCs, with Omicron being the first to develop dominant sub-VOCs worldwide. These sub-VOCs, which either replace or circulate concurrently, indicate a shift from host adaptation to immune escape from infection- and vaccine-induced memory responses. The BA.1 and BA.2 sub-VOCs of Omicron emerged with spike (S) protein mutations, jeopardizing the efficacy of vaccines. However, Omicron sub-VOCs develop mutations beyond spike, indicating S-independent adaptations that may be crucial for Omicron dominance of SARS-CoV-2.
About the Study
In the present study, researchers proposed a model where the earliest host innate immune responses significantly contribute to SARS-CoV-2 transmission by influencing whether interactions with the initial cells in the airways result in productive infection.
Overall, the study’s results demonstrate that Omicron variants of SARS-CoV-2 enhance evasion of the innate immune system by increasing the expression of viral proteins, suggesting that the earliest host innate immune responses are crucial for SARS-CoV-2 transmission. Viruses with an improved ability to evade or antagonize innate immunity, such as increased ORF6 and N expression, are more likely to be transmitted as they can avoid triggering or shutting down host responses that suppress this earliest replication. The team speculates that enhanced innate immune antagonism upon infection outbreak due to a higher viral load and inflammation may lead to increased disease occurrence.