Strategies Used by SARS-CoV-2 to Evade the Innate Immune System in an Evolutionary Perspective

Abstract

By the end of 2019, the COVID-19 pandemic, resulting from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), had diffused widely across the globe, with 770 million infected individuals and over 7 million deaths reported. In addition to its high infectivity and pathogenicity and its rapid mutation rate, the unique capacity of SARS-CoV-2 to circumvent the immune system has also contributed to the widespread nature of this pandemic. SARS-CoV-2 elicits the onset of innate immune system activation and initiates antiviral responses once it has infected the host. While battling the host's immune responses, SARS-CoV-2 has established many countermeasures to evade attack and clearance. As the exploration of SARS-CoV-2 continues, substantial evidence has revealed that the 29 proteins synthesized by the SARS-CoV-2 genome are integral to the viral infection process. They not only facilitate viral replication and transmission, but also assist SARS-CoV-2 in escaping the host's immune defenses, positioning them as promising therapeutic targets that have attracted considerable attention in recent studies. This review summarizes the manner in which SARS-CoV-2 interfaces with the innate immune system, with a particular focus on the continuous evolution of SARS-CoV-2 and the implications of mutations.

Keywords: Omicron; SARS-CoV-2; innate immune evasion; interferon.

Figure 1

SARS-CoV-2 structure and evolution. (a) Schematic representation of the genome of SARS-CoV-2. (b) Phylogenetic tree of SARS-CoV-2 VOCs and Omicron sublineages. ‘*’ is used to emphasize that this region has significant importance in gene structure or function.

Figure 2

Heatmap analysis of spike protein mutation sites in recent Omicron epidemic variants BA.2.86, BA.2.87.1, EG.5.1, JN.1, and XBB.1.5. The blue squares represent mutation sites; the grey squares indicate the absence of mutations.

Figure 3

Schematic diagram of the mechanism by which SARS-CoV-2 evades innate immunity. SARS-CoV-2 proteins that target individual pathways are highlighted in red.