The P681H mutation in the Spike glycoprotein confers Type I interferon resistance in the SARS-CoV-2 alpha (B.1.1.7) variant
Lista, M. J.; Winstone, H.; Wilson, H.; Dyer, A.; Pickering, S.; Galao, R. P.; De Lorenzo, G.; Cowton, V.; Furnon, W.; Suarez, N. M.; Orton, R.; Palmarini, M.; Patel, A. H.; Snell, L. B.; Nebbia, G.; Swanson, C. M.; Neil, S.
Show abstract
Variants of concern (VOCs) of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) threaten the global response to the COVID-19 pandemic. The alpha (B.1.1.7) variant appeared in the UK became dominant in Europe and North America in early 2021. The Spike glycoprotein of alpha has acquired a number mutations including the P681H mutation in the polybasic cleavage site that has been suggested to enhance Spike cleavage. Here, we show that the alpha Spike protein confers a level of resistance to the effects of interferon-{beta} (IFN{beta}) in lung epithelial cells. This correlates with resistance to restriction mediated by interferon-induced transmembrane protein-2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is necessary for comparative resistance to IFN{beta} in a molecularly cloned SARS-CoV-2 encoding alpha Spike. Overall, we suggest that in addition to adaptive immune escape, mutations associated with VOCs also confer replication advantage through adaptation to resist innate immunity.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion 97%
- Engineering, Decoding And Systems-Level Characterization Of Chimpanzee Cytomegalovirus 97%
- Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses 96%
Similar papers in this journal
- The polybasic cleavage site in the SARS-CoV-2 spike modulates viral sensitivity to Type I IFN and IFITM2 98%
- The P681H mutation in the Spike glycoprotein escapes IFITM restriction and is necessary for type I interferon resistance in the SARS-CoV-2 alpha variant 98%
- The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13 97%
Similar papers in this journal
- Genome-scale CRISPR screening reveals host factors required for ribosome formation and viral replication 96%
- The zinc finger antiviral protein ZAP destabilises viral transcripts and restricts cytomegalovirus 96%
- Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration 96%
Similar papers in this journal
Similar papers in this journal
- Structural features stabilized by divalent cation coordination within hepatitis E virus ORF1 are critical for viral replication 97%
- The ER membrane protein complex is required to ensure correct topology and stable expression of flavivirus polyproteins 96%
- The Relative Binding Position of Nck and Grb2 Adaptors Dramatically Impacts Actin-Based Motility of Vaccinia Virus 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.