Our manuscript on #sarscov2 variant mutations in N is now out in @PLOSPathogens
bit.ly/3n8nO5W
If you are at #KSRNAVirus22 you can talk to 1st author Bryan Johnson about it (probably wearing boots & maybe shorts).
A thread on the paper:
bit.ly/3n8nO5W
If you are at #KSRNAVirus22 you can talk to 1st author Bryan Johnson about it (probably wearing boots & maybe shorts).
A thread on the paper:
Bryan noticed several mutations in N at pos 203-204, notably a RG->KR found in alpha and omicron & R->M in delta.
The KR mutant in WA1 augmented replication in respiratory cells and disease in vivo.
R203M mutant had similar in vitro phenotype.
The KR mutant in WA1 augmented replication in respiratory cells and disease in vivo.
R203M mutant had similar in vitro phenotype.
We found that the KR mutation increases N phosphorylation and augments viral RNA expression.
This corresponds with larger lesion and antigen staining despite similar titers in vivo.
This corresponds with larger lesion and antigen staining despite similar titers in vivo.
We also found gsk3 kinase inhibitors were less effective against the KR mutant.
Finally the disruption of the original RG motif appears critical as an alanine mutant (AA) had similar results.
Finally the disruption of the original RG motif appears critical as an alanine mutant (AA) had similar results.
Overall, the results suggest positive selection occurs in the 203-205 region of N and augment #SARSCoV2 infection and pathogenesis.
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