Why Simulate a Virus
Our group's computer simulation of a virus attracted much interest and lead to many questions that we were asked. Here are five of the questions with answers in layman's terms.
1. What is a virus:
A virus is a small particle made of a protein shell that contains genetic material. The shell transports the genetic material until it encounters a host cell, for example riding in small droplets in the air until it is absorbed by the respiratory tract of a person, in the case of influenza virus. Upon contact with a cell the virus latches on to the human; here viruses differentiate themselves since some can dock better to animal cells and others to human cells; some can both. When the virus attaches to the cell, the docking sends a signal in the cells, typically to engulf the virus as a measure to "eat" it or destroy it, and here the virus outsmarts the cell -- before the virus coat is dissolved and digested by the cell, the virus manages to inject its genetic material into the cell and thereby infect it. The infected cell is very much ruled by the viral genetic material, which instructs the cell either right away or sometimes years later to produce viruses, the coat proteins and the genes that go inside them. Usually after a while the infected cell is so full of viruses that it bursts and the viruses go on on their dangerous business, each of them looking for a new cell to invade and infect. The multiplication factor can be huge so that quickly many cells are infected. The immune system may have learned to recognize the virus or the infected cells before they produce too many viruses, and destroy them. In fact, humans have learned to deal with many viruses through vaccination: injection of damaged viral components to "teach" the immune system how to recognize a particular virus. But it is sometimes difficult for our immune systems to recognize viruses, particularly since viruses have an extremely rapid life cycle and hence an extremely rapid evolution which permits them to outpace the immune system by generating new forms. This is why we need a new influenza immunization every fall. Naturally, scientists want to understand the inner working of a virus, in particular, the dynamics of the infection process, the most crucial step in the life cycle of a virus. Many viruses, for example polio viruses, dengue fever virus, human papilloma virus (which is a leading cause of cervical cancer in women), adenovirus (which causes flulike symptoms), have been imaged in atomic level detail such that they can be not only looked at, but also through simulation in a computer, be seen as they move and infect cells.
2. What is it about the virus' makeup that caused it to be difficult to recreate until now?
While viruses are extremely small, a millionth of an inch, they are composed of millions of atoms, which poses a challenge to simulate in a computer program simply due to their size. But with computer technology rapidly increasing such systems can now be simulated for the first time, at least for a very short time span in the life of a virus. Also, imaging using X-rays has recently been used for the first time to see the genetic content of a virus along with its shell, so the entire virus could be followed in its motion.
3. What was your motivation? Public Health or biological advancement?
Both. First, one needs to understand the enemy to beat him. We need to know how the surface of a virus that docks onto cells and we need to know the dynamics of the process by which an initially very stable virus shell is triggered to disassemble and fuse its genetic content with that of the cell. The best way to do this is to look at how it happens and that is what we are doing right now, except that we do not use a real microscope or an X-ray microscope, but rather a computer microscope. But the real goal is to learn to prevent viral infections by finding out where one can interfere with the infection process, using antiviral drugs. Those are chemicals that target for example the viral shell and hinder its assembly or disassembly.
4. How could this accomplishment assist public health officials? Especially those fighting to help contain bird flu virus?
What we know right now on the bird flu virus is the pattern of its evolution that may lead it soon to dock also well to human respiratory tract cells. Researchers see that the virus is already close in this regard. With the ability to look at viruses on the computer, we could try to replay the evolution of the Spanish flu virus as it jumped the species barrier turning from an animal pest into a human pest. Our own work sets the ground for understanding and recognizing what we see. However, currently the influenza virus is too large for computer simulations and it is too amorphous to be imaged at the atomic level, so these techniques cannot yet be applied to this problem.
5. Any concern about the possibility of this technology falling into the wrong hands?
Science is a world wide activity of many individuals; it does not really exist well sheltered behind a security fence, so the knowledge is gained by all at the same time, in a way. The computer could be used one day for good and bad purposes to design a "super virus", but also, more likely, will be applied to use viruses for technical and medical benefits. I think the answer is yes, as with all technologies, even though at present the technical advance is still feeble and very few are capable of simulating entire virus particles.