SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion

Abstract

Coronavirus disease 2019 (COVID-19) has caused an unprecedented global crisis and continues to threaten public health. The etiological agent of this devastating pandemic outbreak is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by delayed immune responses, followed by exaggerated inflammatory responses. It is well-established that the interferon (IFN) and JAK/STAT signaling pathways constitute the first line of defense against viral and bacterial infections. To achieve viral replication, numerous viruses are able to antagonize or hijack these signaling pathways to attain productive infection, including SARS-CoV-2. Multiple studies document the roles of several non-structural proteins (NSPs) of SARS-CoV-2 that facilitate the establishment of viral replication in host cells via immune escape. In this review, we summarize and highlight the functions and characteristics of SARS-CoV-2 NSPs that confer host immune evasion. The molecular mechanisms mediating immune evasion and the related potential therapeutic strategies for controlling the COVID-19 pandemic are also discussed.

Keywords: COVID-19; SARS-CoV-2; antivirals; immune escape; immune evasion; non-structural proteins.

Figure 1

An overview of the SARS-CoV-2 non-structural proteins which contribute to host immune escape (in red boxes). (A) Pathogen-associated molecular patterns (PAMPs) of the virus are recognized by various immune cells (macrophages, monocytes, neutrophils, dendritic and epithelial cells). Upon infection, these immune cells recognize foreign viral antigens and molecules (PAMPs) via pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs)—thus stimulating cytokines and IFNs, and subsequently inducing host immune responses. (B) Type I and type III IFNs are produced and bind to their specific cell surface IFN receptors—thus activating JAK/STAT signaling to promote IFN-stimulated genes (ISGs) to achieve antiviral responses. (Adapted from Park et al. [22]).