Omicron variants evolve strategies to evade T-cell immunity
Context:
A study recently published in the Proceedings of the National Academy of Sciences(PNAS) found that the SARS-CoV-2 virus encodes multiple viral factors that modulate major histocompatibility complex class I (MHC I) expression in the host cells. The MHC I plays an important role in alerting the immune system to virally infected cells. The MHC I molecules are expressed on the surface of all infected cells.
Points to Ponder:
- The SARS-CoV-2 virus can elude CD8 T cells, which help to reduce viral load and clear infections by identifying and destroying infected cells but cannot prevent infection.
- The SARS-CoV-2 virus encodes numerous viral components that affect major histocompatibility complex class I (MHC I) expression in host cells, according to a study published in the Proceedings of the National Academy of Sciences (PNAS).
- By displaying antigens on the surface of infected cells, MHC I plays a vital function in alerting the immune system to virally infected cells.
- The SARS-CoV-2 virus has evolved numerous mechanisms to limit MHC I expression, whereas the influenza virus does not, specifically in infected cells, and differs between viral strains.
- MHC I suppression is mediated by several viral gene products and only affects infected cells. This method does not result in generalized immunodeficiency but rather represents a specialized survival mechanism for SARS-CoV-2.
- Throughout the pre-Omicron variant-of-concern evolution, the ability to lower MHC I expression has remained unaltered.
- When compared to the ancestral strain and other variants, Omicron subvariants (BA.1, BA.2.12.1, XAF, and BA.4) demonstrated a “superior capacity” to inhibit MHC I levels on the surface of virus-infected cells. This helps the virus-infected cells to survive in the host longer and to establish a safe niche for long-term replication.
- Omicron subvariants are better at avoiding detection by killer T cells and neutralizing antibodies, making it difficult for the immune system to remove the infection.
- The researchers discovered common mutations in the E protein (T9I) that are shared by all Omicron subvariants studied and greatly increase the degree of MHC I downregulation. This demonstrates the universal ability of all SARS-CoV-2 strains to drive cell-intrinsic decrease of MHC I expression within infected cells, as well as the superior ability of the Omicron subvariants to acquire MHC I evasion capacity.
- The biological mechanisms and effects of Omicron variants’ greater MHC I inhibition on infection and illness remain unknown.
- Antivirals or antibody therapy may be required to remove the virus’s persistent reservoirs.
