The role of SARS-CoV-2 accessory proteins in immune evasion

Abstract

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-β by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNβ signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.

Keywords: Accessory proteins; Immune evasion; ORF; SARS-CoV-2.

Fig. 1

A diagram illustrates the mechanisms the SARS-CoV-2 virus uses to evade the innate immune response. SARS-CoV-2 has employed various strategies to block innate immune responses and promote effective replication. To develop new vaccines and therapeutic strategies against recently emerging variants, it is necessary to comprehend how SARS-CoV-2 influences innate immunity. [NOTE: IFN: Interferon; STAT1/ 2: Signal transducer and activator of transcription 1/ 2; JAK 1: Janus kinase 1; ISG: interferon-stimulated gene; NPC: nuclear pore complex; ISRE: Interferon-sensitive response element; MAVS: Mitochondrial antiviral signaling; TOM70: Translocase of outer mitochondrial membrane 70; IKK: inhibitor of nuclear factor kappa B kinase)-related kinase; TRAFs: tripartite-motif protein 25 (type I and type II IFN-inducible E3 ligase); RIG-1: retinoic acid-inducible gene I (Type-1 Interferon Pathway); TRIM 25: Tripartite Motif Containing 25; IRF3: Interferon regulatory factor 3].

Fig. 2

Interaction of ORF9c with cellular proteins.