Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4
The Middle East respiratory syndrome coronavirus uses DPP4/CD26 as receptor for cell entry. Soluble recombinant DPP4 can block MERS-CoV infection in cell culture and in animal models and might hold promise as antiviral. Furthermore, endogenous soluble DPP4 in plasma might reduce MERS-CoV dissemination in infected individuals. Therefore, we addressed whether and how MERS-CoV can acquire resistance…
MERS-CoV utilizes DPP4/CD26 as a receptor for cell entry. By employing a VSV encoding the MERS-CoV spike protein, researchers found that viral variants with mutations L507I and L507H in the receptor binding domain of the S protein can reduce binding to soluble DPP4, yet still allow robust entry into cells with high levels of DPP4.
These mutations confer resistance to soluble DPP4 while maintaining entry into cells with high DPP4 expression, but reducing entry into cells with low DPP4 expression. Additionally, polymorphisms L507F/R/P found in MERS-CoV sequences from patients show even more pronounced resistance to soluble DPP4. Overall, naturally occurring mutations in the MERS-CoV S protein can help the virus resist soluble DPP4 binding while still being able to spread effectively in cells and tissues with high DPP4 levels.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
