A new research by scientists at the Weill Cornell Medical College report that a new technology have been developed by them which allows them to watch how HIV proteins behave on the virus’ surface. This is significant as it may contribute in knowing how it infects human cells.
The news about their discovery is described in details in the October 8 issue of science. A part of the study was also published the same day in Nature.
Dr. Scott Blanchard, an associate professor of physiology and biophysics at Weill Cornell, and one of three co-lead authors on the Science study said that this novel technology platform will open new possibilities that will help in finding a way to prevent the HIV infection. He also added that by making the movement of HIV visible, one can follow in real time, how the surface proteins on the virus behave. It can possibly tell us what we need to know to prevent fusion with human cells. If we know how to prevent the viral entry of HIV into immune cells, we are already half way through.
Through this study, the scientists have tried to show that now there is a means to obtain real-time images of what happens on the surface of the HIV particles. The same information can also be used to screen the impact of drugs and antibodies that can shut it down.
There is a desperate need to find solution to prevent HIV infection. This deadly disease has killed more than 70 million people worldwide. Dr. Blanchard opined that if this technology works in HIV management, it can also be applied in decoding the infection process of other viruses.
Dr. Blanchard collaborated with Dr. Walther Mothes, a HIV specialist at the Yale University School of Medicine, and with Dr. James Munro, an assistant professor at Tufts University School of Medicine.
An imaging technique that uses fluorescence to measure distance on molecular scale – single-molecule fluorescence resonance energy transfer (smFRET) imaging was adapted by Dr. Blanchard to study viral particles. His team worked on developing fluorescent molecules also known as fluorophores and the same were inserted into the virus’s outer covering. With two of these fluorophores in place, smFRET imaging can be used to visualize how the virus proteins change conformation.
The technology was used by the team to study motions of proteins on the surface of the HIV virus. It is known that these proteins are key to the virus’s ability to infect human immune cells carrying CD4 receptor proteins that help the HIV bind to a cell. The over surface of HIV consists of three gp120 and gp41 proteins positioned close together. These are referred to as “trimers,” and open up like a flower in the presence of CD4. Thus they expose the gp41 subunit that paves way for the mechanism that causes infection. It was observed that there are 10-20 such trimers on the surface of each HIV particle. They mutate very fast and evade typical immune responses. Since, the body is unable to mount an effective immune response, it is challenging for scientists to develop vaccines for HIV. The researchers studied proteins from two different strains of HIV. It was seen that the gp120 proteins’ virus particles changed shape constantly and that the timing and nature of their movements were both similar and distinct.
This knowledge is significant because, it answers the first big question which is how opening of the envelope trimer is triggered. It has been so long believed in the scientific community that the particles remain in one conformation until they come across a CD4-positive cell. But, this study shows that the proteins change even when no CD4 was present, which means that they change shape all the time. This and many significant discoveries about the process of infection were made in this study.
Dr. Blanchard opined that the practical outcome from this technology is that now we have begun to understand how the biological system of HIV moves. The focus now is on improving the technology so that imaging precision is achieved to make broadly effective therapies.