The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance

Area of Science:

• Virology
• Molecular Biology
• Epidemiology

Background:

• The SARS-CoV-2 Lambda variant (a variant of interest) has emerged and spread across South America.
• Key virological characteristics and evolutionary pathways of the Lambda variant remain largely unelucidated.

Purpose of the Study:

• To investigate the virological features and evolutionary traits of the SARS-CoV-2 Lambda variant.
• To identify specific mutations responsible for the Lambda variant's infectivity and immune evasion properties.

Main Methods:

• Utilized pseudovirus systems to assess viral infectivity and antibody neutralization.
• Analyzed spike protein mutations, including T76I, L452Q, and the unique RSYLTPGD246-253N deletion.

Main Results:

• The Lambda variant's spike protein exhibits enhanced infectiousness compared to other variants, attributed to T76I and L452Q mutations.
• The RSYLTPGD246-253N deletion confers significant antibody evasion and enhances antibody-mediated infection.
• This deletion creates a new N-linked glycosylation site, though the associated glycan is not essential for the observed virological properties.

Conclusions:

• The RSYLTPGD246-253N mutation is strongly associated with the Lambda variant's increased transmissibility and immune escape.
• Findings suggest this mutation is a key driver of the Lambda variant's dominant spread in South America.