Just what is a virus, and where did they come from? Considering that the field of virology dates back to the mid 1800s, it may come as a surprise that these questions are still controversial, and yet, they are. Recently, a team of French scientists discovered viruses of a size and complexity never seen before, and this discovery has been highly disruptive to the controversy.
The French team, composed of the Aix-Marseille University School of Medicine's Jean-Michel Claverie and Chantal Abergel, among others, has been instrumental in the discovery of very large DNA viruses such as the mimiviruses, pandoraviruses, and the recently identified pithovirus.
Although these large viruses vary in terms of their appearance and the exact size of their genomes, they have in common a set of properties that makes them fascinating. Firstly, they all infect amoeba, despite being isolated under conditions as disparate as 30,000-year-old permafrost and a lake in Chile. Secondly, their DNA genomes are large enough to rival bacterial genomes and are orders of magnitude more complex than any of the viral genomes previously identified. Thirdly, these genomes contain genes that have never before been observed in viral genomes, genes for such things as protein synthesis machinery, which most viruses leave for the host cell to produce. Fourthly, and perhaps most fascinatingly, as much as 93 percent of the genomes of these large viruses bears no resemblance to any known life form; with their purpose entirely unknown, the so-called "ORFan" genes of these viruses are truly terra nova in the virology world.
Because these recently discovered viruses have so many properties never before seen in viruses, scientists have been forced to rethink their definition for what a virus truly is. Since the mid 1800's when viruses were first distinguished from other infectious agents such as bacteria and fungi, scientists have used so-called "negative criteria" for defining viruses, identifying them by what they are not rather than what they are. Indeed, viruses were defined as "filterable agents" that could pass through the filters that infectious agents such as fungi and bacteria could not. Viruses were also defined by their inability to replicate in the absence of host cells and their dependence on the host cell for metabolic functions such as protein synthesis.
Naturally, the discovery of large viruses with properties so different from conventional viruses calls into question the general definition of "virus" that has been taught for over a hundred hears. No longer can viruses be called "filterable agents," always smaller than bacteria, as some of these viruses are larger than bacterial cells. Viruses also cannot be said to lack protein synthesis machinery in their genomes, as these large viruses do code for some of this machinery.
Perhaps even more important than the the definition of "virus" is the origin of these infectious agents. Unfortunately, the sands of time have not been kind to the type of information virologists would need to determine what the first viruses looked like, as viruses evolve so rapidly that common ancestry is quickly obscured by mutation. Based on their dependence on host cells for replication, viruses could have arisen in two different ways. Many virologists hypothesize that viruses could have arisen by accretion, evolving from a "selfish gene" called a transposon that somehow escaped from a host cell, gaining new genetic material and more complex function over time. Other virologists propose that viruses are actually the remnants of fully functional cells that have shed genes and self-sufficiency over time, becoming parasites wholly dependent on other cells for their replication.
These two competing hypotheses, one of accretion from a selfish gene transposon and the other of reduction from a full cell, both have compelling arguments behind them. However, the discovery of very large, complex viruses with expansive genomes suggests that the reduction-from-cells hypothesis may be closer to the truth. Because these viruses code for components of protein synthesis machinery and other gene products that logically they should not require, it is reasonable to think these viruses are in transition, having yet to lose all the gene products they do not need for replication in their existence as intracellular parasites. It is much harder to believe that such complexity arose by accretion from a selfish gene.
Surely, virologists still have much to learn from these very large viruses. Since much of their genomes are not annotated and bear no resemblance to any known gene, uncovering potential function for the genes that make up these "black box" genomes will be difficult. However, understanding how these large viruses work and uncovering more details about their gene functions will allow virologists to better distinguish just where life ends and the ever-mysterious viral world begins.