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SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance

By Al_Sharpton_for_President follow Al_Sharpton_for_President   2021 Aug 12, 5:15pm 108 views   1 comment         share      


Summary

SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.

Highlights

Lambda S is highly infectious and T76I and L452Q are responsible for this property

Lambda S is more susceptible to an infection-enhancing antibody

RSYLTPGD246-253N, L452Q and F490S confer resistance to antiviral immunity

Discussion

In this study, we demonstrated that three mutations, the RSYLTPGD246-253N, L452Q and F490S mutations, respectively confer resistance to the vaccine-induced antiviral immunity. Additionally, the T76I and L452Q mutations contribute to enhanced viral infectivity. Our data suggest that there are at least two virological features on the Lambda variant: increasing viral infectivity (by the T76I and L452Q mutations) and exhibiting resistance to antiviral immunity (by the RSYLTPGD246-253N, L452Q and F490S mutations).

Virological experiments demonstrated that a large 7-amino-acid deletion, the RSYLTPGD246-253N mutation, does not affect viral infectivity but is responsible for the resistance to the vaccine-induced neutralization as well as an NTD-targeting NAb. Additionally, molecular phylogenetic analyses showed that the transition of the proportion of the Lambda variant harboring a large 7-amino-acid deletion, the RSYLTPGD246-253N mutation, is associated with the increase of the effective population size of this variant. Therefore, the emergence of the RSYLTPGD246-253N mutation could be one of a driving forces behind the spread of this variant in the human population. In fact, here we showed that the Lambda S is more resistant to the vaccine-induced antisera than the Lambda+N246-253RSYLTPGD S derivative. Our results suggest that the resistance of the Lambda variant against antiviral humoral immunity was conferred by the RSYLTPGD246-253N mutation. Importantly, the RSYLTPGD246-253N mutation overlaps with a component of the NTD “supersite” (Chi et al., 2020). Altogether, these observations suggest that the NTD “supersite” is immunodominant and closely associate with the efficacy of the vaccine-induced neutralization, and further support the possibility that the emergence of the RSYLTPGD246-253N mutation triggered the massive spread of the Lambda variant.

https://www.biorxiv.org/content/10.1101/2021.07.28.454085v1.full

1   Tenpoundbass   2021 Aug 12, 5:22pm  

Could it be the Vax is all about making a large portion of our population chronically ill, and in need of Universal Obamacare for all some? Those not on board will be the dreaded anti-maskers.

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