Using single-molecule fluorescence imaging, UNSW Medicine researchers have developed a biosensor to track dynamic protein-protein interactions in real-time between the human immunodeficiency virus (HIV) and its host. This sensor can measure the intimate interactions of host proteins with the HIV-1 capsid – a protein shell that safeguards the virus against host attack.
In a paper published in ACS Applied Materials and Interfaces, the researchers detailed the design of their new biosensor, which was developed in collaboration with the Kirby Institute. The first author of this study is fourth year PhD student in the School of Medical Sciences, Mr Derrick Lau.
This biosensor is so sensitive, it can detect the binding of single protein molecules. “We can count the number of molecules that bind to the capsid,” says Single Molecule Science researcher and study lead, Associate Professor Till Böcking.
To find out how host proteins interact with the viral capsid, the researchers designed a device using HIV-1 capsid tubes as binding platforms for host proteins. The tubes are made by assembling the protein building blocks of the HIV-1 capsid into an extended honeycomb network, as they do in nature. “This is important because some host proteins recognise the larger pattern of the capsid, but previous sensors typically used small fragments of the capsid,” explains Associate Professor Böcking.
The HIV-1 virus gains access into the cell, and then makes its way to the nucleus to establish infection. During this time, the host has mechanisms to detect the intruder and destroy it, while the virus uses different ways to avoid detection and destruction.
“More sensitive methods to monitor and measure these dynamic interactions between viruses and their hosts will help us understand how they evade immune defences and establish infection,” Associate Professor Böcking says.