Sugar-Coated Quantum Dots Illuminate Viral Infection

University of Leeds (U.K.)-led chemists have developed a new method for making fluorescing quantum dots (QDs) coated with a key biological sugar molecule, and using them to study how viruses like Ebola and HIV attach to proteins on the surface of healthy cells (Angewandte Chemie, doi: 10.1002/anie.201600593). The authors say that their new technique for studying these ligand–protein interactions could improve scientists’ understanding of how viruses attach to cell membranes, which may eventually lead to treatments that block viral attachment and prevent infection.  

The researchers looked at two nearly physically identical cell-surface proteins called DC-SIGN and DC-SIGNR that bind to mannose (a type of sugar) on the surface of HIV and Ebola viruses. Despite their similar structure, DC-SIGN and DC-SIGNR have different viral binding affinities—meaning that the proteins grab onto the viruses with different strengths. To find out why the binding affinities of DC-SIGN and DC-SIGNR vary, the researchers used an assay called QD Förster resonance energy transfer (FRET), which combines the sensitive, ratiometric readouts of FRET with the stable and bright fluorescence of QDs.

Using a new method developed at the University of Leeds, the scientists prepared mannose-coated fluorescing QDs that mimic HIV and Ebola viruses and added them to solutions of DC-SIGN and DC-SIGNR. Results from their QD FRET assays revealed that both DC-SIGN and DC-SIGNR attach to the virus via four sites, but the orientation of these sites is important to the strength of the bond. Their work, the authors say, not only provides insight into the protein-ligand interactions of HIV and Ebola infections, but also helps establish the QD FRET assay as a “rapid, sensitive technique for probing structure and thermodynamics of multivalent protein-ligand interactions.”