Thread by @SystemsVirology

A new preprint "An emerging SARS-CoV-2 mutant (='the California variant', B.1.427/429) evading cellular immunity and increasing viral infectivity", from The G2P-Japan consortium, organized by my lab, is out at @biorxivpreprint. Please RT 1/7
biorxiv.org/content/10.110…

During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. 2/7

The sensitivity of naturally occurring SARS-CoV-2 variants to 'humoral immunity (=neutralizing antibodies)' has recently been investigated. However, the impact of viral mutations to human leukocyte antigen (HLA)-restricted 'cellular immunity' remains unaddressed. 3/7

In this study, we demonstrate that two recently emerging mutations in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. 4/7

Not only the escape from the HLA-A24-restricted cellular immunity, these mutations also reinforce the affinity to viral receptor ACE2. And notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. 5/7

Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic. 6/7

To our knowledge, this is the first study directly demonstrating a major SARS-CoV-2 variant, “the California variant (B.1.427/429)”, can evade an HLA-restricted cellular immunity. Please feel free to ask any questions and retweet! 7/7

PS - "The G2P-Japan consortium" is the abbreviation of "The Genotype to Phenotype Japan consortium", an apparent homage to the G2P-UK:
ukri.org/news/national-…

Although the scale of our consortium is much smaller than the UK version (now only 5 labs joining!), we also aim to reveal the "genotypes" of SARS-CoV-2 variants and demonstrate their "phenotypes". Looking forward to having chances for collaboration. Not limited to Japan!!