Uncovering Novel Viral Innate Immune Evasion Strategies: What Has SARS-CoV-2 Taught Us?

Abstract

The ongoing SARS-CoV-2 pandemic has tested the capabilities of public health and scientific community. Since the dawn of the twenty-first century, viruses have caused several outbreaks, with coronaviruses being responsible for 2: SARS-CoV in 2007 and MERS-CoV in 2013. As the border between wildlife and the urban population continue to shrink, it is highly likely that zoonotic viruses may emerge more frequently. Furthermore, it has been shown repeatedly that these viruses are able to efficiently evade the innate immune system through various strategies. The strong and abundant antiviral innate immunity evasion strategies shown by SARS-CoV-2 has laid out shortcomings in our approach to quickly identify and modulate these mechanisms. It is thus imperative that there be a systematic framework for the study of the immune evasion strategies of these viruses, to guide development of therapeutics and curtail transmission. In this review, we first provide a brief overview of general viral evasion strategies against the innate immune system. Then, we utilize SARS-CoV-2 as a case study to highlight the methods used to identify the mechanisms of innate immune evasion, and pinpoint the shortcomings in the current paradigm with its focus on overexpression and protein-protein interactions. Finally, we provide a recommendation for future work to unravel viral innate immune evasion strategies and suitable methods to aid in the study of virus-host interactions. The insights provided from this review may then be applied to other viruses with outbreak potential to remain ahead in the arms race against viral diseases.

Keywords: RNA-RNA interactions; RNA-protein interactions; SARS-CoV-2; innate immune evasion; protein-protein interactions; viral-host interactions.

FIGURE 1

Viral evasion mechanisms and methods for investigation (example with SARS-CoV-2). Common methods of innate immune evasion by viruses include the modification of 5′-end, double membrane vesicles (DMV) to shield viral RNA (vRNA) and interference with host innate immune factors. 5′-end modifications may be determined using biochemical assays; formation of DMV can be detected by electron microscopy and immunofluorescence localization. The host innate immune response may be interrupted through protein-protein interactions, RNA-RNA interactions and viral (protein)-host (RNA)/viral (RNA)-host (protein) interactions, attenuating interferon (IFN) and interferon stimulated gene (ISG) expression. Figure created using BioRender.com.