How can we define a virus? Formulating an answer to this question is extremely difficult. Why? The ambiguity of whether or not a virus is living, which is made challenging by the complexities associated with defining life itself.
Various scientists have explored the question "What is Life?" in detail - notably E. Schrödinger, and other scientists, including A. Pross, have readdressed the same question since. There are a couple of key features of a virus which can be noted when we consider its definition:
- viruses are found in all forms of cellular life
- viruses have genomes which enable the coding of proteins through nucleic acids, alongside appropriate enzymes to convert RNA to DNA and replicate
However, as things currently stand, viruses do not seem to be able to carry out this conversion alone, instead using a host cell which contains membrane-bound organelles - this includes ribosomes for protein synthesis.
Many different views form as to whether a virus is alive or not based on the definition that one holds of life in the first place. Here are a few examples:
- a virus is not alive because it cannot reproduce alone, and needs a host cell to be able to do so
- a virus could be described as a 'capsid-encoding organism', with organism suggesting it could be alive or that there is life within the virus
- if something can be 'killed' then it must have shown signs of life to begin with, otherwise it cannot truly be classified as dead - hence, if a virus isn't alive, can we kill a virus?
- the discovery of large viruses from 1992 onwards (identified fully in 2003) may support the living hypotheses
Large Viruses? Mimiviruses? Giruses?
Let me introduce you to something which many people do not know about - the existence of large viruses, otherwise known as mimiviruses (sometimes referred to as giruses). Mimiviruses can be damaged by smaller viruses (often referred to as 'virophages'). Virophages are viruses with double stranded DNA (dsDNA) and quite short amino acid sequences. They have similar function mechanisms to bacteriophage viruses which can damage bacteria.
One example of a virophage is Sputnik which uses the larger virus as a site upon which they can replicate themselves - this presents the case that the larger virus have a high chance of being living; otherwise, this process would not be possible - essentially, these larger viruses are being used as host cells are in most cases.
However, as with any piece of research, it's important to consider the other side of the argument. It is key to note that these large viruses tend to take over other organisms such as amoeba in the first instance, and then the large virus manufacturing system is attacked by the smaller virus, hence producing/replicating the smaller virus (virophage) instead.
Crossing the borderline between living and non-living?
Mimiviruses appear to bridge the borderline and hence triggers questions as to whether viruses can be at the forefront of evolution. Some mimiviruses are larger than bacteria (considered living organisms due to the other characteristics they possess). An average mimivirus diameter is around 750nm (see Figure 1), with a significant proportion of this being made up of fibres that extend from its capsid. There are beliefs that these mimiviruses could have been alive before since they hold almost all of the requirements for enabling the synthesis of proteins, and hence are very similar to bacteria. Despite this, they do not synthesise the majority of proteins. However, they are able to code for some enzymes - herein lies the proposed bridge between the living and non-living worlds by some.
Furthermore, this leads to possible inferences that there is an evolution pathway between mimiviruses, cells, and organisms as we know them. They could have evolved through the loss of genetic information and hence provide a critical link in determining whether viruses are alive, or if they used to be alive!
Superinfection Exclusion
Is something alive if it cannot be killed? Viruses have the capability to protect organisms against other viruses through inherited resistance. Retroviruses are a key example of these which can induce immunity through superinfection exclusion where the virus can prevent the organism from contracting a further infection of the same virus, or one similar to it. To use an analogy, this process can be likened to traditional vaccination whereby through exposing someone to a dead, inactive or weak form of a pathogen can induce the immune system to respond and hence upon secondary infection, there are already memory B cells present which can quickly trigger the production of plasma cells, and destroy the pathogen - overall, inducing long term immunity.
If the same virus or a very similar virus tried to re-infect the immune system, a response could be coordinated. One key study exemplifying this was proposed by Muñoz-González et al. who demonstrated how this occurred in the phenomenon of superinfection exclusion in wild boar with relation to swine fever.
Viruses are intracellular and found in all forms of cellular life - hence placing them as the most abundant entity that is of a biological nature found on Earth! Retroviruses inject a DNA copy of their genome into host cells and can then replicate - they are responsible for around half of the genomic sequences found in some organisms, including humans. The nucleic acid material present in the genomes would enable protein encoding if the viruses have the facility to do so (such as single stranded RNA (ssRNA), double stranded RNA (dsRNA) and DNA dependent on the virus).
Many viruses fall into the category of non-producers because they are unable to carry out active transport and other key processes. Ribosomes are not found in the majority of virus entities, although some viruses do contain membrane-bound organelles or entities. Without ribosomes, protein translation would seem unfeasible. However, as mentioned, mimiviruses can code for some enzymes hence showing that it is indeed possible within an entity classified as a virus to synthesise proteins.
Most viruses have actually been found to be able to synthesise or encode for at least one protein that is found in its own capsid.
RNA: The Main Method of Communication
RNA regulates and coordinates all of the matters related to life within organisms. Some genes found in viruses are found in other organisms since it is believed by many that viruses could have evolved from living cells. Contrarily there are many cases of genes in viruses that are unrelated to genes found in living cells.
Implication? Perhaps viruses existed before and were hence able to reproduce themselves - showing another quality of life. Furthermore, viruses still containing enzymes able to aid DNA synthesis from RNA adds to this argument.
Villareal and Witzany propose that there are three levels on which there are interactions between entities:
- between RNA
- between viruses
- between cells/organisms
This would mean that RNA is a major communication network - reinforced by the knowledge that RNA can move into and out of the nucleus in eukaryotes through nuclear pores (DNA is unable to do this). Hence, RNA appears to be a more viable way of communicating information to other areas such as within a cell for protein synthesis by taking the sequence to a ribosome.
The Evolution of Viruses: Gaining Certain Characteristics at the Expense of Others
Viroids are amongst the earliest entities known to display some qualities of life. They are smaller than a virus, comprising of just a nucleic acid with no protein coat, and are the smallest known pathogen which is able to infect an organism. Some believe that RNA could produce, and aid life, and that life was built upon structural concepts instead of genetic information during this time. Most currently believe that RNA alone would be insufficient to produce life though, and that instead the viruses have to be reliant on host cells.
Some qualities of life could have been lost in a similar manner to how mitochondria and other (now) organelles became organelles. Mitochondria used to be bacteria with around 3000 genes, but now only contain approximately 37 genes, and are endosymbionts (found within others most of the time (at least)) (see Figure 2). Being the site of aerobic respiration, mitochondria are key. Their decreasing number of genes is closely related to a decrease in the level of independence. The same logic follows that viruses could have once been alive and fully functioning, but lost this through the process of evolution somewhere along the line.
However, in both cases we see critical entities in biological systems. In the case of mitochondria, allowing for the synthesis of ATP to act as an immediate energy source. Contrarily with viruses, to infect us and cause illness, or possibly treat some illnesses - see more on virotherapy in the future. One example is a clinical trial looking at treating types of lung cancer using viruses since they replicate selectively. Hence it is believed that this method would lead to fewer (undesirable) side effects for the patient due to the drug being more specialised and the treatment being targeted.
Can we answer the question... yet?
The question as to whether viruses are alive or not does not have a definitive answer due to the lack of a concrete definition of life. However, as presented in the evidence above, there are cases to suggest the following:
- viruses could have been alive at one stage in the past
- mimiviruses and hence other potential future viruses show some signs of life - could viruses eventually show all of the key signs of life?
- viruses are not considered alive by many due to their requirement of a host cell in order to replicate
It is important to note the significance of viruses in the current society though (especially given the SARS-CoV-2 pandemic) and how although they are often perceived by the general public to be entities that infect people and cause disease, there are many viruses that could be key for maintaining good health, and could be used to treat various conditions in the future.
I hope that this article was useful in providing a brief overview to a very complex and highly questioned topic! Check back tomorrow for the next article: Molecular Scissors: CRISPR/Cas9 Technology!
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