Are all viruses really viruses?

 

The discovery of always smaller bacteria and always bigger viruses are challenging the concept of viruses as we know it. Should we go back and rethink about the definition itself and about the way that viruses have evolved?

The history of virology begins at the end of the 19th century with the discovery that the responsible of the tobacco mosaic disease could pass through the filters used to retain bacteria. At the time it was not clear what these infectious agents were and they were commonly indicated as “infectious living fluids”. At the same time the term “virus” was introduced, as it means “poison” in Latin. Later, it was recognised that viruses were actually particulate composed of proteins and nucleic acids that could pass the filter used to retain bacteria. Furthermore, only in the 1930s, with the technological development of electron microscopy, the structure of these agents could be observed.

Nobel prize winner André Lwoff, one of the firsts to propose a definition of virus, affirmed that “viruses are viruses”, to stress that they are a distinct evolutionary lineage, not linked to any kingdom of life (Lwoff, 1957, J. Gen. Microbiology). Besides the historical definition, related to their small size, viruses were accordingly defined as “strictly intracellular and potentially pathogenic entities with an infectious phase, and (1) possessing only one type of nucleic acid, (2) multiplying in the form of their genetic material, (3) unable to grow and to undergo binary fission, (4) devoid of a metabolic pathway capable of producing energy; (5) dependent on the host cell translation machinery (this point was added retrospectively as the cellular process of translation was not yet understood when Lwoff wrote this definition).

Some of these points were disproved over the time through new discoveries, as e.g. Hepatitis B Virus can incorporate in the virion a copy of its genome under the form of DNA and RNA, and it is considered a DNA virus, but it replicates through a RNA intermediate.

The recent discovery of giant viruses as Mimi-, Mega-, Pandora- and Phytoviruses made the classical definition of virus even more shaky.

Picture(1)

Fig.1 Comparison of Mimivirus and Pandoravirus particles with Influenza virus.

These newly revealed viruses (Fig. 1) are indeed bigger than some small bacteria, definitely disproving the historical definition of viruses as being filterable biological entities. Interestingly, they also encode for proteins implicated in translation as aminoacyl-tRNA synthethases and some translation factors. This discovery is not in conflict with the fact that viruses are dependent on host cell translation, as complete translation machinery in a virus has never been found to date, but the existence of such a ‘virus’ (or virus ancestor) is no more Science fiction. Some scientists are therefore proposing that (at least) giant viruses may have evolved from cells through a gradual process of loss of essential functions that forced them to parasitism. If this turns out to be provable, the next question would be: what about other viruses? In particular, (i) did small dsDNA viruses come from an evolutionary process that was characterized by a progressive but eventually massive loss of functions (and a shrinkage of their capsid)? (ii) Did other viruses, as RNA viruses, have also evolved from cells through loss of genes? Or are unrelated viruses (as small dsDNA viruses or RNA viruses versus giant viruses) the result of different evolutionary lineages?

In our opinion, at the moment it is hard to imagine RNA viruses to have evolved from a cell as no cells with RNA genomes have been observed to date. Furthermore, the existence of both ‘types of viruses’ is compatible. Adapting Lwoff thoughts, we could state that some viruses are still really viruses (e.g. RNA viruses), while some aren’t (e.g. big dsDNA viruses). The term girus (a contraction of giant virus) was created also to stress this difference, as giant viruses have unique genes, which are not found in other forms of life, and they are therefore proposed to be part of a fourth domain (or super kingdom) of life. Those unique genes are unlikely to have been acquired from their host cells. Of course, this doesn’t exclude that viruses from other evolutionary lineages have acquired some genes from their host.

Then, where does the boundary to distinguish giant viruses from intracellular parasites could be placed? Eventually, the ongoing concomitant identification of smaller and smaller parasites and bigger and bigger viruses seems to possibly fill in the gap between the viral and the cell worlds, which was unimaginable only some time ago.

Differently to other organisms that live within a cell, viral genome comes out of the particle when the particle enters the cell. Consequently, a virus is an obligate intracellular parasite that releases its genome in the host cell at the beginning of its life cycle and is then rebuilt within the cell itself.

The virus definition has changed over time and it is still evolving. As Virology is a recent Science (it is only just over 100 years old) and we have characterised only a small portion of the enormous number of existing viruses, it is predictable that we have not reached the final definition of virus yet.

If you want to know more about it, see:

Lwoff, The Concept of VirusJ. Gen. Microbiology (1957), 17, 239-253.

M.G. Fischer et al., Giant virus with a remarkable complement of genes infects marine zooplankton. PNAS (2010), 107, 19508-19513.

D. Arslan et al., Distant Mimivirus relative with a large genome highlights the fundamental features of Megaviridae. PNAS (2011), 108, 17486-17491.

N. Philippe et al., Pandoraviruses: Amoeba Viruses with genomes up to 2.5 Mb reaching that of parasitic Eukaryotes. Science (2013), 341, 281-286.

Legendre M, Bartoli J, Shmakova L, Jeudy S, Labadie K, Adrait A, Lescot M, Poirot O, Bertaux L, Bruley C, Couté Y, Rivkina E, Abergel C, Claverie J-M. Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. PNAS (2014), published ahead of print March 3, 2014, doi:10.1073/pnas.1320670111

Abergel C, Claverie JM. Les virus sont-ils vraiment des virus? Virologie (2013), 17, 217-228.

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