Preprint: SARS-CoV-2 variants do not evolve to promote further escape from MHC-l recognition, Moriyama et al, 2022

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SARS-CoV-2 variants do not evolve to promote further escape from MHC-l recognition

Summary

SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection.

By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that VOCs retain similar MHC-I downregulation capacity compared to the ancestral virus.

However, VOCs exhibit a greater ability to suppress type I IFN than the ancestral virus.

Although VOCs possess unique mutations within the ORF8 gene, which suppresses MHC-I expression, none of these mutations enhanced the ability of ORF8 to suppress MHC-I expression.

Notably, MHC-I upregulation was strongly inhibited after the ancestral SARS-CoV-2 infection in vivo.

Collectively, our data suggest that the ancestral SARS-CoV-2 already possesses an intrinsically potent MHC-I evasion capacity, and that further adaptation by the variants was not observed.

 

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Prof. Iwasaki has provided a summary on Twitter:

 

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Prof. Iwasaki has provided a summary on Twitter:

Continued:

 

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From the News Medical article prof. Awasaki links to:

SARS-CoV-2 variants are not evolving to escape from T cell-mediated immunity

Conclusions

Presumably, SARS-CoV-2, like many other viruses, has developed ways to avoid the efficient MHC-I mediated antigen presentation to CD8+ T cells, as they play a vital role in the host adaptive immune response.

Upon investigating whether SARS-CoV-2 variants shut down the host MHC-I system, the authors discovered that it was not the case rather, the ability to reduce MHC-I expression remained unchanged throughout VOC evolution. Conversely, SARS-CoV-2 VOCs have evolved to limit the host type I interferon response. Therefore, it is highly likely that the SARS-CoV-2 ancestral strain was fully optimized to escape from CD8+ T cell-mediated immunity and was under no evolutionary pressure to further optimize its immune evasion strategy.

This finding also raised the possibility that SARS-CoV-2 utilizes multiple redundant mechanisms to suppress MHC-I expression to ensure escape from CTL killing. Additionally, unlike influenza A or Epstein-Barr virus, it impairs the priming of CD8+ T cells.

Taken together, the study data demonstrated the ability of SARS-CoV-2 to potently avoid the MHC-I-mediated antigen presentation to CD8+ T cells and the role of ORF8 in its efficient replication and transmission.