Under the outer shell of various viruses, such as the HIV virus and viruses that cause cancer, there is another shell that plays a central role in the infection processes of cells. New research sheds light on the properties of the shell and how we can crack it
"The Institute" magazine
Shell can be hard, soft, flexible or tough. To find out the degree of hardness of a shell, you can press it with a force that gradually increases, and follow its reactions to the pressure, until the point where it will break. But how to perform this experiment on a shell whose properties change, and whose size does not exceed a thousandth of the thickness of a human hair?
This is the challenge facing scientists studying the envelope properties of retroviruses, such as the HIV virus that causes AIDS, and other viruses that cause various types of cancer. Under the outer shell of the virus is another shell, which is actually a kind of template of proteins that plays a central role in the infection processes of cells by retroviruses.
In retroviruses, significant internal change processes take place on their way "from childhood to adulthood". They leave the host cell that created them as primary viruses, when they are immature and non-infectious, and only then do they go through a maturation process at the end of which they are able to infect other cells.
The structure changes with "maturing"
Observations using an electron microscope showed that in this ripening and "maturing" process, the thickness of the protein shell under the virus envelope is reduced, and that its structure changes. Dr. Itai Russo, from the Department of Structural Biology at the Weizmann Institute of Science, examines the mechanical properties of this shell at different stages of the virus's development, and his findings raise several questions regarding the way in which retroviruses infect the body's cells.
Dr. Russo and research student Nitzan Kol used an atomic force microscope (AFM) to examine how much force can be applied to the virus shell until it breaks. An atomic force microscope is based on gentle physical contact between a tiny nano-needle in front of the material being examined.
A computerized system, which receives the needle's reports, registers a precise mapping of the surface of the sampled bone. The institute's scientists chose to leave the needle in one place, press in gradually, and examine the results. In this way, we examined the shells of retroviruses of a strain that infects mice and is not dangerous to humans, in two developmental stages: when the virus is in its "childhood" stage, and after it has gone through the maturation process. To their surprise, they discovered that the protein pattern beneath the virus envelope is characterized by great rigidity and very little flexibility, something that makes you fragile, like an eggshell.
Very tough in the early stage
The shell structure of an immature virus was even more rigid: more than twice as compared to the shell of a mature virus. The hardness of the shell of the mature virus, which far exceeds the hardness of the cell membranes, puts to the test the accepted concept regarding the way in which viruses penetrate cells, according to which, in the first stage of penetration, the virus shell unites with the cell membrane.
Since the existence of a hard shell under the virus envelope was not known until recently, some basic questions were not asked or examined such as: at what stage does the shell collapse and what is the source of the energy required to break it?
"We may have to go back and rethink certain aspects of the model for cell infection by retroviruses," says Dr. Russo. "We still don't know why retroviruses change their mechanical properties during their life cycle. Understanding the reason for this, as well as understanding the relationship between the changes in the hardness of the shell during the life of the virus and its biological activity, are the goal of our current research."
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