SARS-CoV-2: A Master of Immune Evasion

Abstract

Viruses and their hosts have coevolved for a long time. This coevolution places both the pathogen and the human immune system under selective pressure; on the one hand, the immune system has evolved to combat viruses and virally infected cells, while viruses have developed sophisticated mechanisms to escape recognition and destruction by the immune system. SARS-CoV-2, the pathogen that is causing the current COVID-19 pandemic, has shown a remarkable ability to escape antibody neutralization, putting vaccine efficacy at risk. One of the virus’s immune evasion strategies is mitochondrial sabotage: by causing reactive oxygen species (ROS) production, mitochondrial physiology is impaired, and the interferon antiviral response is suppressed. Seminal studies have identified an intra-cytoplasmatic pathway for viral infection, which occurs through the construction of tunneling nanotubes (TNTs), hence enhancing infection and avoiding immune surveillance. Another method of evading immune monitoring is the disruption of the antigen presentation. In this scenario, SARS-CoV-2 infection reduces MHC-I molecule expression: SARS-CoV-2’s open reading frames (ORF 6 and ORF 8) produce viral proteins that specifically downregulate MHC-I molecules. All of these strategies are also exploited by other viruses to elude immune detection and should be studied in depth to improve the effectiveness of future antiviral treatments. Compared to the Wuhan strain or the Delta variant, Omicron has developed mutations that have impaired its ability to generate syncytia, thus reducing its pathogenicity. Conversely, other mutations have allowed it to escape antibody neutralization and preventing cellular immune recognition, making it the most contagious and evasive variant to date.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases

“…Based on our present research experience [ 126 ], dealing with the SARS-CoV2 virus in the laboratory is an exceptionally challenging and unique experience when compared to other similar RNA viruses. Potential mechanisms such as increased transmissibility [ 127 ], immune escape [ 128 ], diagnostic failure [ 129 ], and reduced effectiveness of vaccines have resulted in the development of novel variants [ 130 ] that contain rather significant mutations all of its four protein domains spike (S), envelope (E), membrane (M) and nucleocapsid (N). Mutations in these protein domains have been shown to alter an individual strain’s infectivity and transmissibility in the community.…”

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

“…Continuous mutation of the SARS-CoV-2 SP impacts innate immune responses and could further increase virulence, pathogenicity and immune evasion of the virus given that one of the strategies by which SARS-CoV-2 evades immune response is through cytokine shock [ 48 , 49 ]. Noteworthily, mutations in the SARS-CoV-2 ORF8 (which could modulate the SP during transmission) have been associated with inhibition of the Major Histocompatibility Complex (MHC)-1 stimulation, thus leading to the low production of cytotoxic T cells (CD8 + T cells) [ 50 , 51 , 52 ]. In our study, the SARS-CoV-2 Delta variant SP had the highest potential of stimulating the NF-κB pathway in macrophages to induce inflammatory cytokines in the monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) when compared with the Wuhan strains or D614G variants.…”

The immunogenetics of COVID-19

“…Histopathological examinations have revealed hyaline membranes, mononuclear and macrophage infiltration of air gaps, and thickening of the alveoluminal wall (Bösmüller et al 2021 ; Mason 2020 ; Pandey and Agarwal 2020 ). SARS-CoV-2 also disrupts normal immune responses, leading to an impaired immune system and uncontrolled inflammatory responses in severe and critical patients with COVID-19 (Tay et al 2020 ; Rubio-Casillas et al 2022 ). These individuals show lymphopenia, lymphocyte activation and dysfunction, granulocyte and monocyte abnormalities, elevated cytokine levels, and a rise in immunoglobulin G (IgG) and total antibodies (Gibson et al 2020 ; Lippi and Plebani 2020 ; Yang et al 2020a ).…”