On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses

Abstract

Host immunity can exert a complex array of selective pressures on a pathogen, which can drive highly mutable RNA viruses towards viral escape. The plasticity of a virus depends on its rate of mutation, as well as the balance of fitness cost and benefit of mutations, including viral adaptations to the host's immune response. Since its emergence, SARS-CoV-2 has diversified into genetically distinct variants, which are characterised often by clusters of mutations that bolster its capacity to escape human innate and adaptive immunity. Such viral escape is well documented in the context of other pandemic RNA viruses such as the human immunodeficiency virus (HIV) and influenza virus. This review describes the selection pressures the host's antiviral immunity exerts on SARS-CoV-2 and other RNA viruses, resulting in divergence of viral strains into more adapted forms. As RNA viruses obscure themselves from host immunity, they uncover weak points in their own armoury that can inform more comprehensive, long-lasting, and potentially cross-protective vaccine coverage.

Keywords: RNA viruses; SARS-CoV-2 variants; adaptation; host immunity; viral escape.

Figure 1

Summary of three sources of immune pressure during viral infection and viral proteins that act is immune modulators: (A) viral dsRNA is detected by immune sensing PRRs, triggering expression of IFN genes by phosphorylation and nuclear import of IRF-3. NS1 is a potent inhibitor of IRF-3 activation by binding viral dsRNA and preventing recognition by RIG-I. SARS-CoV-2 NSP6/13 are capable of binding TBK1 to suppress phosphorylation and activation of IRF-3, whereas ORF6 blocks its nuclear import factors; (B) neutralization of viral surface antigens by host antibodies, which is attenuated by adaptations in the surface antigen; (C) presentation of T cell epitopes by HLA class I molecules on the surface of the infected cell, which can be undermined by adaptations in HLA-restricted epitopes in a viral protein. (Created with BioRender.com).