Nano-Crystals May Lead to New Treatments for HIV, Ebola Virus
Crystals mimic the shape of HIV and Ebola virus to show how they bind to cells.
How HIV and Ebola viruses attach to cells has always been a mystery, but researchers from the University of Leeds have discovered how to block the interaction of cells, instead of destroying pathogens, in order to treat these viruses.
“Until now, how these viruses attach to cells was a 'black box' to chemists,” said lead study author Yuan Guo “We knew that the viruses were interacting with healthy cells, but the way in which they bound together was still a mystery.”
During the study, researchers used quantum dots, nano-sized crystals that are approximately a millionth of a millimeter in size. These crystals mimic the shape of the viruses and act as technological stand-ins in experiments to show how they bind to cells.
Quantum dots are fluorescent crystals that are dependent on the size of the crystal to determine its emitted light color. Furthermore, it has emerged as an advanced type of fluorescent probe for biomolecular and cellular imaging, which makes them useful for studying how viruses spread.
By using a new technique that was developed for the study, the researchers coated the quantum dots in sugar first, in order to allow them to bind to cells.
“We often only hear about sugar in a negative light, about how consuming it is bad for our health,” said study co-author Dr. Bruce Turnbull. “But there are many different types of sugars that play a vital role in human biology. In fact, all of our cells are coated in sugar and they interact with other cells by proteins binding with these sugars. Indeed, the reason why we have different blood types is because of the different types of sugar coating on our red blood cells.
“Viruses also attach to the surface of healthy cells through interactions between proteins and sugars. These interactions are weak individually, but can be reinforced by forming multiple contacts to offer the viruses a 'way in'. We want to understand what factors control this binding process and, eventually, develop a range of inhibitors designed to target specific viral bindings.”
The results of the study showed that 'DC-SIGN' and 'DC-SIGNR', 2 cell surface sugar binding proteins originally thought to be nearly indistinguishable, bound to the surface sugars of the Ebola and HIV viruses, allowing them to spread.
“These proteins are like twins with different personalities,” said lead co-author Dr. Dejian Zhou. “Their physical make-up is almost identical, yet the efficiency with which they transmit different viruses, such as HIV and Ebola, varies dramatically and the reason behind this had been a mystery.
“Our study has revealed a way to differentiate between these proteins, as we have found that the way in which they bind to virus surface sugars is very different. They both attach via 4 binding sites to strengthen the bond, but the orientation of these binding pockets differs.”