Virus variants: when is it right to worry?

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Original article: Il caso delle varianti virali: quando é giusto preoccuparsi?, by Ilaria Bellini

To have a fair view of reality, sometimes, we need to change our point of view.

How many times have you heard this sentence? How many times were you able to do it? Well, today, my dear readers, even us from the Microbiologia Italia’s team, we ask you for an extra effort.

All the information coming from everywhere scares us: English, Brasilian, or South-African virus variants, the increased virus transmission, etc. We are confused, and the more frequent question people keep asking is: when is it right to worry? What can we define as physiological and dangerous?

In this article, we will try to clarify the situation. This time, we will do it differently. We will stop being human, but just for a moment, and we will try to tell a new story by using a different point of view: the one from the virus.

Let’s start.

With the virus’ eyes

The viruses are defined as forced intracellular parasites. What does it mean? They are not able to live outside an organism’s cells. Although they are very clever, Mother Nature didn’t give them all the necessary tools to be completely autonomous. For this reason, what they don’t have, they take it from others.

How do they take it? Through infection. The viruses steal the precious tools of the complex organisms using them to replicate, evolve and stay in the circle of life. It is the only way to prevent extinction. Evolution, however, is a law that applies to everyone, so also, the host organisms developed some defense mechanisms against the damage the virus provokes. In this way, the immune system was born, and with it, the battle that has come down to us: the adapting fight.

This war is based on two fronts:

  • Set up of stronger and precise weapons to destroy the enemy;
  • Implementation of careful strategies to evade the other’s defenses.

The strongest carries on, while the weakest stays behind, and sometimes it disappears. We are well aware of what the mammals (which also includes humankind) had to do to arrive here today, but maybe we should know more about the strategies used by the virus.

The virus ability to adjust

After a systematic observation of their enemy for years, the viruses comprehend the best methodology to approach a new host and survive it, so it completely embraces natural selection. Our dearest Darwin (Fig.1) taught us that the individuals of the same species tend to variate their genotype (genetics) and so the phenotype (morphology and functionality), based on the interaction with the environment. Random genetic mutations give variability. This brings the individuals to have some more favorable characteristics in a particular environment, determining an adaptive survival and reproduction advantage. Therefore, during the generations following the onset of mutations, are “chosen” those that are better than others.

Picture of Charles Darwin, father of evolutionary biology.
Figure 1 – Picture of Charles Darwin, father of evolutionary biology [Bibliography: wikipedia.org]

For every organism and the viruses, the primary aim is to carry on their species and not harm the host. They need us to live, but since we – like them – tend towards conservation, our defense mechanisms have forced viruses to be more flexible and adapt to different environments. In this way, they use mutations as the basic strategy, and here we are with the virus variants.

How did they do it?

  1. The correction mechanism (proofreading) is very low efficient: all organisms have a tool that repairs the possible errors during the DNA synthesis. Usually, viruses hold less efficient and accurate systems, and sometimes they don’t have any. The result is that the error rate is one nucleotide out of thousands of DNA bases and, for some viruses with an RNA genome, the rate is one mutation out of hundred bases. More mutations mean more possibility of selection.
  2. High replication rate: viruses and bacteria replicate very fast. It allows them to synthesize more DNA/RNA, to have a high probability of mutation, and to develop convenient variants.

Why didn’t we choose this strategy?

We are very complex organisms. Therefore we have longer biological cycles, fewer cycles of DNA synthesis, a very effective correction system. Thus we are genetically more stable with a lower mutation frequencies rate. Our complexity has probably enabled us to focus on more sophisticated strategies to attack and defend ourselves in this war. For this reason, our advantage was to build protection barriers (epidermis, mucus, etc.) to create an immune cells army.

This doesn’t mean we don’t accumulate mutations and changes; on the contrary, we are also the result of selective pressure. It is sufficient to think of people immune to some pathology (such as sickle cell anemia) caused by known or unknown mutations. The concept is the same, but for the above mention reasons, the modifications are not frequent.

The viruses mutate

It is physiological that the viruses mutate; it’s in their nature. Often it is a random mechanism, so clearly, not all the mutations have a happy ending. They can be: convenient, unfavorable, or cannot generate improvements. On the other hand, the more the viruses interact with an enemy, the more they replicate, the more they study the mechanisms and find the flaw in the system. The more we witness virus variants.

The positive mutations generate the following modifications :

  • improve the affinity to the viral receptor, increasing the infection mechanism efficiency;
  • increase the stability of the virus particle in the environment; therefore, they can lengthen their half-life and make a more productive transmission;
  • develop resistance to antiviral drugs;
  • modify the target structures of the antibodies, so they can’t be attacked and destroyed;
  • boost their fitness to implement their diffusion and replication.

Do all the viruses variate in the same way?

Unfortunately, not. The RNA viruses accumulate more mutations than the DNA ones, and at the same time, among the RNA viruses, some mutate more frequently than others. For instance, the flu virus is an RNA virus that mutates so often to force us to change the vaccine formulation every year. HIV (Fig.2) is an example of an RNA virus that it can mutate so often to have the ability to determine virus variants even in the same person. Therefore, prevent from creating an efficient vaccine and having adequate therapy.

Example of the HIV virus variants in the blood
Figure 2 – Example of the HIV in the blood [Bibliography: www.geneproof.com]

Why do we have so many virus variants?

Even our ill-famed Sars-Cov-2 is an RNA virus, and as such, it mutates. That’s why we keep hearing about the variants. After a year of pandemic and the infection of millions and millions of people, we could easily say that the variants’ existence is pretty normal. And we’ll tell you more, going over the scientific literature with a fine-tooth comb, you’ll find plenty of Sars-Cov-2 mutations.

When is it right to worry?

At this point of the article, it is probably clear that we have to accept that the viruses mutate and that we’ll keep hearing about this toping for months. When is it right to worry? When these mutations result conveniently, therefore, the virus could:

  • be more contagious;
  • give more severe forms of the disease;
  • not be neutralized by the antibodies;
  • become resistant to the therapies;
  • become immune to the vaccine.

It is precisely these last two points that we should focus on.

If we had had adequate therapy, an efficient vaccine, and herd immunity, the other three points wouldn’t be so scary. The question is quite complex since we don’t have perfect therapy to cure Covid-19, but we do have vaccines that have great results to build the group immunity.

What can happen?

If I don’t get vaccinated, what does it change for you?” Often we read or hear similar sentences; maybe, now we can reply better with “IT DOES CHANGE FOR ME.”

One of the worst prospects that might occur is that a part of the population gets vaccinated, while the other is not, letting the virus spread. The virus will keep going from an individual to another, mutating until a new virus variant will arrive, vaccine-resistant, and so we will be at the starting point.

So, what does it change?

It changes, and maybe it is better even for you, to change your point of view.

Martina Calderato

Bibliography

  • Everett Clinton Smith, Nicole R. Sexton and Mark R. Denison. “Thinking Outside the Triangle: Replication Fidelity of the Largest RNA Viruses”. 2014.
  • http://www.infezioniobiettivozero.info/8-infezioni/114-varianti-virus-sars-cov-2-quando-fenomeno-naturale-e-atteso-diventa-notizia
  • https://it.wikipedia.org/wiki/Selezione_naturale#:~:text=La%20teoria%20della%20selezione%20naturale,favorite%20(%22selezionate%22)%20quelle
  • Ella Hartenian, Divya Nandakumar, Azra Lari, Michael Ly, Jessica M. Tucker, and Britt A. Glaunsinger. The molecular virology of coronaviruses. 2020.

Picture bibliography

  • https://www.rinnovabili.it/ambiente/politiche-ambientali/covid-19-e-malattie-infettive-il-ruolo-di-ecosistemi-e-ambiente/
  • https://it.wikipedia.org/wiki/Charles_Darwin
  • https://www.geneproof.com/geneproof-hiv-type-1-hiv-1-pcr-kit/p1129

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