Are viruses alive?

In this new video from Virus Watch, I tackle the thorny question of whether viruses are alive.

Plenty of people have offered their opinon on this question. The results of a poll I’ve had here on virology blog shows that people are divided on the answer.

But I’m sure I have a good answer to this question.

TWiV 289: Vinny and the capsids

On episode #289 of the science show This Week in VirologyVinny and the capsids answer listener questions about the definition of life, state vaccination laws, the basic science funding problem, viral ecology, inactivation of viruses by pressure, and much more.

You can find TWiV #289 at www.microbe.tv/twiv.

Can a virus be revived?

PithovirusIn Carl Zimmer’s New York Times article describing the recovery of the giant virus Pithovirus sibericum from the Siberian permafrost, he used the words revive and resurrect. Can a virus be restored to life?

The headline of the article read ‘Out of Siberian ice, a virus revived‘. Within the body of the article, Zimmer wrote ‘From Siberian permafrost more than 30,000 years old, they have revived a virus that’s new to science’, and later considered the ‘risk of an outbreak of resurrected viruses’. Both words mean ‘restore to life’.

When most people say ‘virus’ they usually mean the very small virus particle that infects cells. Virus particles are not living: they are assemblies of protein, nucleic acid, and sometimes lipids that do nothing until they infect a cell. That is why they are called obligate intracellular parasites. In the case of Pithovirus, infectious virus particles were present in the frozen sample that were able to infect amoeba in the laboratory.

To say that a virus was revived or resurrected is wrong, although I understand that the idea of bringing anything back to life has a great deal of general appeal. The key fact in this story is that the infectivity of the virus particle was maintained for over 30,000 years in the Siberian permafrost. I realize that this does not make for compelling headlines, but mine would have been: ‘Infectious virus recovered from Siberian ice after 30,000 years’. I suspect that Zimmer might understand this, but as he’s told me before, sometimes it’s much easier (and requires fewer words) to write something for the non-scientist that is not quite right.

Even virologists confuse the living with the non-living. When Paul Bieniasz and his laboratory reported that they had reconstituted an infectious retrovirus from viral sequences in the human genome, they used the phrase ‘the resurrection of this extinct infectious agent’.

A virus particle is not alive, but a virus infected cell certainly is living. A virus can be viewed as an organism with two phases, a non-living virus particle, or virion; and an infected cell, which is alive.  This definition solves the problem of whether a virus is alive or not, a subject of much debate here and elsewhere. Even if we use this terminology, the use of resurrect and revive to describe viral infectivity is still wrong, because virus particles cannot be brought back to life – they are not alive to begin with.

The virus and the virion

The illustration at left depicts a virion – the infectious particle that is designed for transmission of the nucleic acid genome among hosts or host cells. A virion is not the same as a virus. I define virus as a distinct biological entity with five different characteristics. Others believe that the virus is actually the infected host cell.

The idea that virus and virion are distinct was first proposed by Bandea in 1983. He suggested that a virus is an organism without a cohesive morphological structure, with subsystems that are not in structural continuity:

Viruses are presented as organisms which pass in their ontogenetic cycle through two distinctive phenotypic phases: (1) the vegetative phase and (2) the phase of viral particle or nucleic acid. In the vegetative phase, considered herein to be the ontogenetically mature phase of viruses, their component molecules are dispersed within the host cell. In this phase the virus shows the major physiological properties of other organisms: metabolism, growth, and reproduction.

According to Bandea’s hypothesis, the infected cell is the virus, while the virus particles are ‘spores’ or reproductive forms. His theory was largely ignored until the discovery of the giant mimivirus, which replicates its DNA genome and produces new virions in the cytoplasm within complex viral ‘factories’. Claverie suggested that the viral factory corresponds to the organism, whereas the virion is used to spread from cell to cell. He wrote that “to confuse the virion with the virus would be the same as to confuse a sperm cell with a human being”.

If we accept that the virus is the infected cell, then it becomes clear that most virologists have confused the virion and the virus. This is probably a consequence of the fact that modern virology is rooted in the study of bacteriophages that began in the 1940s. These viruses do not induce cellular factories, and disappear (the eclipse phase) early after cell entry. Contemporary examples of such confusion include the production by structural virologists of virus crystals, and the observation that viruses are the most abundant entities in the seas. In both cases it is the virion that is being studied. But virologists are not the only ones at fault – the media writes about the AIDS virus while showing an illustration of the virion.

Those who consider the virus to be the infected cell also believe that viruses are alive.

…one can conclude that infected eukaryotic cells in which viral factories have taken control of the cellular machinery became viruses themselves, the viral factory being in that case the equivalent of the nucleus. By adopting this viewpoint, one should finally consider viruses as cellular organisms. They are of course a particular form of cellular organism, since they do not encode their own ribosomes and cell membranes, but borrow those from the cells in which they live.

This argument leads to the assumption that viruses are living, according to the classical definition of living organisms as cellular organisms. Raoult and Forterre have therefore proposed that the living world should be divided into two major groups of organisms, those that encode ribosomes (archaea, bacteria and eukarya), and capsid-encoding organisms (the viruses).

BANDEA, C. (1983). A new theory on the origin and the nature of viruses Journal of Theoretical Biology, 105 (4), 591-602 DOI: 10.1016/0022-5193(83)90221-7

Forterre, P. (2010). Defining Life: The Virus Viewpoint Origins of Life and Evolution of Biospheres, 40 (2), 151-160 DOI: 10.1007/s11084-010-9194-1

Viruses and the tree of life

tree-of-life-with-genomeAre viruses living entities? I don’t believe so, but it’s an engaging question for debate. On a recent episode of “This Week in Virology” we concluded that it’s somewhat of a futile argument because everyone has their own view; perhaps our time is better spent studying viruses than discussing whether or not they are alive. The authors of ‘Ten reasons to exclude viruses from the tree of life’ cogently disagree:

We believe that considering viruses alive or not is not just a matter of opinion, contrary to a commonly held view, but rather is a matter of inference and logic starting from any given definition of life

Following is my distillation of why the authors believe that viruses are not alive, and why they do not represent ancient lineages of the tree of life.

1. Viruses are not alive
Throughout history there have been many definitions of life. Viruses do not meet the criteria for any of them.  They lack any form of energy, carbon metabolism, and cannot replicate or evolve. They are reproduced only within cells, and they also evolve within cells. Without cells, viruses are “inanimate complex organic matter”.

2. Viruses are polyphyletic
In a phylogenetic tree, the characteristics of members of taxa are inherited from previous ancestors. Viruses cannot be included in the tree of life because they do not share characteristics with cells, and no single gene is shared by all viruses or viral lineages. While cellular life has a single, common origin, viruses are polyphyletic – they have many evolutionary origins.

3. There are no ancestral viral lineages
No single gene has been identified that is shared by all viruses. There are common protein motifs in viral capsids, but these have likely come about through convergent evolution or horizontal gene transfer.

4. Because today’s viruses infect phylogenetically distant hosts doesn’t mean that they are ancient
It cannot be proven that early viruses appeared along with the first cells. The problem is that viruses move readily between diverse hosts. Consequently the ability of a virus to infect a particular species could lead to false conclusions about the ancient origin of viruses.

5. Viruses don’t have a structure derived from a common ancestor
Cells obtain membranes from other cells during cell division. According to this concept of ‘membrane heredity’, today’s cells have inherited membranes from the first cells that evolved, and provides evidence that cells are derived from a common ancestor. Viruses have no such inherited structure.

6. Viral metabolic genes originate from cells
Many viral genomes encode proteins involved in energy, carbon, and cellular metabolism. It has been argued that the presence of these genes indicates that viruses are ancestral to cells. Unfortunately, metabolic genes are not present in the ancestors of these viruses. This finding makes it difficult to argue that viruses predate cells.

7. Viral translation genes originate from cells
The mimivirus genome harbors genes encoding elements of the protein synthesis machinery. This observation has been interpreted to mean that viruses did not always rely on cells for translation. However, sequence analysis indicates that these genes are derived from cells by horizontal gene transfer.

8. Viruses steal genes from cells
Viral genomes encode many genes that have no homologues in cells. It has been suggested that viruses influence evolution of cells by donating new genes. Sequence analysis has failed to provide support for this hypothesis. Viruses are ‘gene robbers, not gene inventors and massive gene suppliers’.

9. Most gene transfer goes from viruses to cells
The movement of genes is mainly in the direction of cells to virus. Transfer in the reverse direction is minimal. Therefore viruses have not had a significant role in shaping the gene content of cells. This conclusion is paradoxical because viral genomes are the most abundant on earth.

10. Just because viruses are simple doesn’t mean that they are old
One view of evolution is that it is a process by which simple organisms become more complex. The simplicity of many viruses lead to their placement at the origin of life. This long-standing hypothesis ignores the fact that viral genomes are subject to selective pressure to maintain minimal size to ensure rapid replication rates. The authors conclude that viral simplicity is a consequence of parasitism, not antiquity.

Even though viruses are not living and should not be included in the tree of life, they play an important role in evolution of their cellular hosts by regulating population and biodiversity.

Are you convinced by these arguments? Post a comment and let us know whether you think viruses or living or not.

Moreira, D., & López-García, P. (2009). Ten reasons to exclude viruses from the tree of life Nature Reviews Microbiology, 7 (4), 306-311 DOI: 10.1038/nrmicro2108