Deletion variants (delta82-85 and delta83-86) in the N-terminal region of the nsp1 of a SARS-CoV-2 BA.5.2.1 variant
The non-structural protein 1 (nsp1) of SARS-CoV-2 plays a key role in host innate immuneevasion. We identified two deletion variants (delta82-85 and delta83-86) in the N-terminal region ofthe nsp1 of a SARS-CoV-2 BA.5.2.1 variant recovered from a human patient. To evaluate the functional relevance ofthese mutations, we cloned the mutant BA.5.2.1 nsp1delta82-85 and nsp1delta83-86 and wild-typensp1 proteins in mammalian expression plasmids and performed luciferase reporter-basedassays to assess activation of the interferon and nuclear factor kappa B (NF-kappaB) signallingpathways. Both nsp1delta82-85 and nsp1delta83-86 mutants showed a significant decrease in theirability to inhibit the interferon beta (IFN-B) and NF-kappaB signalling pathway activation. To assessthe relevance of these deletions in the context of SARS-CoV-2 infection, we generatedrecombinant viruses carrying the wild type BA.5.2.1 nsp1 or the BA.5.2.1 nsp1delta82-85 andnsp1delta83-86 deletions in the backbone of WA1 strain. In vitro characterization of therecombinant SARS-CoV-2 viruses revealed that the recombinant viruses containing thensp1delta82-85 and nsp1delta83-86 deletions presented similar plaque size and morphology to thoseproduced by the wild-type rWA1-BA.5.2.1-nsp1 virus, indicating a similar ability of the mutantviruses to spread from cell to cell.