When we contract the flu, AIDS or covid-19, we are not infected by a single variant or sub-variant, but by many. And on top of that, they never stop changing and evolving. Can scientists venture and anticipate these changes?
Influenza, acquired immunodeficiency syndrome (AIDS), hemorrhagic fevers caused by the Ebola virus and covid-19 have something in common: they are diseases caused by RNA viruses. All of them, regardless of the severity of their symptoms, are extremely difficult to eradicate. This fact is closely related to the great evolutionary capacity of the viruses that cause them.
It follows that any effective strategy against RNA viruses must take this evolutionary factor into account. But is it possible to predict how viruses change?
The great viral genetic diversity
We have all become accustomed to hearing that RNA viruses evolve very quickly. That is why we speak quite naturally about variants and sub-variants. However, it is hard for us to get used to the idea that, when we contract the flu or covid-19, our body actually contains an unimaginable number of viruses (which can be on the order of 10¹²) that often have differences in their genomes. In other words: we are never infected by a single variant or sub-variant.
We can visualize the genome of an RNA virus as a chain in which the letters A, C, U, G –which designate the four basic units or nucleotides that make up this molecule– are arranged in a certain order. That order contains the information needed to produce new viruses after infecting a cell. It would be something similar to the meaning given to a text by the order in which the syllables and words follow one another in it. If we alter that order, its meaning will also be changed. Similarly, if we change the nucleotide sequences in a viral genome, viruses with new capabilities may emerge.
Figure showing the mutations that occur during the copying of the viral genetic material and how these give rise to different viruses (Prepared by the author).
RNA virus genomes are about 10,000 nucleotides long on average, so, at least in theory, you can get 4¹⁰⁰⁰⁰ different viruses. However, it must be taken into account that not all combinations of nucleotides make sense, since many of them may not produce viable viruses, in the same way that there are mixtures of words that give rise to meaningless paragraphs.
If, at the time of suffering an infection, a sample of infected tissue was taken and analyzed, in each of those 10,000 letters that, on average, make up the viral genome, the one that predominates in the entire set of viruses that exists in the sample would be observed. . In this way we obtain a sequence, which we can consider the sequence of “our virus”, the one that is harming us at that moment. But that, in reality, corresponds to an average of billions of different sequences.
To make matters worse, these sequences are continually changing because, prior to the generation of a new virus, in a very short time, all the letters that will make up its genome have to be copied. In the process, it is frequent and inevitable that errors occur: they are the so-called mutations.
What drives the evolution of viruses?
In the immense set of viruses that make up viral populations, from time to time one emerges that works better than the rest and that, thanks to the action of natural selection, will increase in frequency. However, evolution is not something deterministic and the best is not always what ends up being imposed. That happens because evolution is also governed by chance.
To begin with, the generation of mutations is a random process, which means that the most advantageous ones are not always available. In addition, not all individuals infected by a virus are equally successful in transmitting it to others, something that will largely depend on their social contacts.
Finally, the number of viral particles that are transmitted between individuals is usually small. This means that in each transmission event a population bottleneck is produced, in which genetic diversity can be greatly reduced.
During an epidemic process, viral evolution involves the alternation of millions and millions of population bottlenecks –-as many as new infections– followed by the subsequent exponential amplification of the virus in each new infected individual.
It is very difficult to integrate all of the above at the population level, which makes it very difficult to predict the direction that an epidemic will take. Viruses are transmitted in a complex environment in which many variables interact that cannot be controlled – some due to the virus itself and others due to circumstances unrelated to it. As a consequence, establishing correlations between the environment, genetic changes and the effects of those changes is not an easy task.
looking for regularities
What we scientists can do is look for regularities in the behavior of viruses, so that it is easier for us to venture how they are going to change. One of the tools we use for this is experimental evolution or, what is the same, reducing the complexity of the real world by carrying out tests in which viruses are propagated under controlled conditions in the laboratory.
In this way, by comparing the initial virus with the one resulting from its evolution under the conditions analyzed, we can learn a lot about the factors that influence the process of its adaptation to environmental changes.
Through this approach, important issues have been studied such as the influence on viral evolution of the number of particles that initiate each infection, the relevance of the frequency with which the virus makes mistakes when copying its genome, the ability of viruses to increase the time that retain their infectivity in the environment or the factors that determine the appearance of mutants resistant to treatment.
Sometimes, the aforementioned studies are not carried out with pathogenic viruses, since their handling has more restrictions than that of other, more innocuous viruses. Although each virus has its particularities, what is intended is to find some type of pattern that can be generalized to a world in which the prevailing is the lack of certainties.
This is basic science, a very valuable tool, but whose results – in this case the design of more effective strategies against viruses – are not always obvious or immediate.
It is highly recommended that our urgency to find solutions does not make us forget that applications do not precede knowledge, but always arise after it.
This article has been published in ‘The conversation‘.
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