Recursive Pathogens

I recently read an article published in Nature letters (link).  The topic of the article is that of a newly discovered pathogen: the virophage. 

The virophage is something completely out of the ordinary, compared to usual pathogens.  Virophages, like viruses, are not actually alive.  They lack their own molecular machinery for reproduction, and must rely on the host's machinery for this purpose.  For a typical virus, this is fairly simple conceptually.  A typical virus hijacks the molecular machinery of the cell, using it to produce viral proteins and induce other behavior advantageous to the virus.  The cell is forced to create new viruses with its own machinery, allowing for the creation and spreading of even more viruses.

In the respect of hijacking a host's machinery, the virophage is no different from a typical virus.  What is atypical, however, is that virophages actually hijack the already hijacked cellular machinery.  That is, virophages require that some other virus has already modified the molecular machinery of a cell in a certain way that the virophage can use it.  The virophage alone cannot infect a cell; it requires both the cell and another virus infecting the cell.

For this matter, it may be wrong to say the virophage infects the cell.  Based on the results of the paper, it seems more accurate to say that the virophage infects the other virus, which happens to reside in a cell.  Infection with virophage caused many of the normal viral components produced to be nonfunctional.  That is, the virophage impeded the spread of the infecting virus.  The virophage actually had a beneficial effect for cells.  Significantly fewer cells died when infected with virus + virophage instead of just virus (virophage + cells was no different than cells alone).

Although this is not too difficult to understand, it's a very different way of thinking.  The common terms "pathogen" and "host" which used to have clear definitions become blurred.  The virophage is not a cellular pathogen, but rather a viral pathogen.  Given that viruses are not alive, this is a paradox: how can something nonliving be a pathogen to something else that is nonliving?  This gets at the very root of what it means to be "alive", which has been hotly debated in the past by people across a wide variety of fields.

I think there are a lot of directions in which this research could go.  For one, it is suggested that virophages are extremely common in oceans, and perhaps elsewhere.  So far, all virophages discovered have come from common cooling towers, so they exist out of the ocean as well.  I wonder how many different kind of virophages there are.  Perhaps we could find a virophage for existing viral human pathogens, although this is probably jumping the gun.

A logical next step is to determine exactly how the virophage is hijacking the other virus.  The nonfunctional viral particles produced are very strange, and it does not seem obvious how they come about. 

Another question that comes to mind is selection advantage and the evolution of virophages.  Consider an extremely virulent virus.  This virus usually kills its host.  For a virus, it is unfavorable to kill off the host, since the host is required for reproduction.  Additionally, it is unfavorable to adversely affect the host significantly.  Generally, very sick people partially quarantine themselves from the rest of the population, namely by bedrest.  It is in the virus' best interest to spread to as many people as possible, and a very sick host cannot do that.  This is partially why the cold virus is so ubiquitous - people rarely get sick to the point of avoiding others, which in turn spreads the virus.  In summation, a highly virulent virus is bad both for the host it infects and the virus itself.

This is where I see a virophage coming in.  Although the virophage is a viral pathogen, in this case, it is actually in the virus' best interest not to be so virulent.  If the virophage prevents the host virus from being so pathogenic, then the end result is that the host virus can spread to more people.  Granted, much less of it is spreading, but considering that only one virus is theoretically needed to start an infection, this reduction may be acceptable.  The virophage is also beneficial to the cell, as cells simultaneously infected with virophage and virus usually do much better than cells infected with only virus.

That's my suspicion anyway.  As stated before, there are a lot of paths this research can take from here, and I only scratched the surface with these ideas.  Time to revise the textbooks.