Evolution of viruses and immunity

Evgeny Kunin, Post-science

There is such a well–known question: what came first - the chicken or the egg? You can ask in the same way: what came first – a virus or immunity? And, as in the question of chicken and egg, neither one nor the other answer can be correct. The correct answer is that they arise simultaneously, in constant interaction, from simpler forms. As soon as viruses or virus–like parasites appeared - and they appeared, apparently, simultaneously with the origin of life – protection against them immediately appeared.

History of virus research

Protection, or rather, vaccines against viruses appeared even before people understood what a virus was. They understood that there were infectious diseases, but they did not see any difference between bacteria, viruses and even some amoebas. Apparently, the first vaccine against smallpox appeared, which the English doctor Edward Jenner created at the end of the XVIII century. In any case, this is the first documented case of research and use of the vaccine. Then, already in the 1870s, another famous event happened - the creation of a rabies vaccine by Louis Pasteur. It worked perfectly and looked like a real miracle: a completely incurable disease that can be prevented and even cured if you start treatment with these vaccines in time.

But at the same time, vaccines were created blindly. There were no ideas that there is some special type of agent that causes these diseases. Such ideas began to appear at the very end of the XIX century. In the 1890s there was a Russian scientist, Dmitry Iosifovich Ivanovsky, a young man who was still preparing to defend his dissertation, nothing particularly remarkable. He researched tobacco diseases and was the first to pay attention to the fact that this disease was transmitted with the juice of diseased plants. That is, the causative agent of this disease somehow passed through filters that do not pass bacteria. Ivanovsky didn't really understand whether it was a living organism or not, he rather thought it was a toxin, although he suspected that this beginning somehow reproduces itself. But, anyway, he was the first to describe such an object, attracted the attention of the scientific community and became, in fact, the founder of virology. And then, quite in a short time, a number of important discoveries were made: it was shown that many diseases are caused by viruses – foot-and-mouth disease, yellow fever, polio, avian sarcoma.

The English bacteriologist Frederick Tuert in 1915 described in his article a group of viruses infecting bacteria, and the French-Canadian microbiologist Felix D'erelle in 1917 described these viruses in detail and gave them the name bacteriophages, that is, ‘bacteria eaters’, because when added to bacteria in the nutrient medium, these viruses create a zone with dead bacteria. Thus, by the end of the First World War, it became clear that there are some tiny agents that make up a very special class of parasites.

Viruses against immunity

Speaking about the confrontation between viruses and bacteria, we can recall such a concept, which is completely officially recognized in biological science and plays a huge role – this is an arms race. It sounds anthropomorphic, but it's an officially accepted term. The whole history of life is an arms race between hosts and parasites. The fact is that any immunity is based on the recognition of one's own and someone else's. The process of fighting viruses and immunity can be illustrated by the famous phrase of the Red Queen from Alice in Wonderland, who said that in order to stay in place, you need to run as fast as possible. For example, what does the now famous CRISPR system do? It borrows the genome of the parasite – not the whole, of course, but a piece long enough that it is definitely (well, almost-almost exactly) not in the genome of the bacterium or archaea itself, and this gives a wonderful result. Viral DNA embedded in the host genome is used to synthesize a special RNA molecule complementary to the viral genome, which actually serves as a vaccine. Special enzymes cut the viral genome at the site of attachment of this RNA and thereby kill the virus.

Such immunity is extremely effective. However, the notorious race turns on: as soon as the virus changes in the corresponding part of the genome, it becomes resistant to the vaccine. And in order to restore immunity, the host must borrow new fragments of the altered viral genome. So this is such a fundamental (since it is based on the central principle in biology – complementarity of nucleic acids) form of this arms race.

There are other ways to fight. Many viruses develop special, so to speak, anti-protective agents. In particular, viruses very often have certain proteins that adapt to the immune system and interfere with it. Very often it happens that the virus captures a component of the host's defense system and uses it against it. This component changes and stops working, but is perceived as working. And in this way, the virus seems to put a stick in the wheels of the host. This is a very common phenomenon. Such an arms race leads to a variety of both viruses and host protection systems. This is the most important factor in generating diversity in the process of evolution.

It is obvious that some viruses adapt to the immune system and continue to fight, and some are defeated. But we don't know anything about these species that existed millions of years ago, but never followed the path of evolution. However, we can reconstruct some ancestral forms that have left offspring that have survived to the present day.

Virus Survival Strategies

It is very important to understand that when we talk about viruses, we are talking about things that are inevitable for any evolving system, about the joint evolution of hosts and parasites. And here you need to understand that the ultimate goal of viruses and parasites in general is not the death of the host. The fitness that is optimized during evolution has nothing to do with killing the host. The virus only seeks to multiply as quickly and efficiently as possible, and it is this ability that is being improved during its evolution. In fact, it is better for him never to kill his hosts at all, for the virus it would be best for his hosts to be happy, so that he himself could reproduce especially efficiently. But the trouble for the virus is that these goals – effective reproduction and preservation of the host's life – often come to a contradiction. And in fact, many viruses lead a "moderate" lifestyle and never kill their hosts. To do this, they have to reduce the intensity of reproduction.

Another strategy is to multiply as much as possible, and when the host dies, move on to another one. The advantage of one or the other strategy depends on the stability of the environment. If the parasite can "foresee" that the host population will be stable and will exist for millions of years, then it is by no means necessary to kill it. If there is a high probability of some catastrophes, which in any case will reduce the host population to zero, then it should be used as quickly as possible and move to another population. I must say that some viruses evolve in such a way as to combine both of these strategies.

In the course of evolution, viruses have developed other ways of survival. They can embed their genome into the host cell and thus live. However, when something bad threatens its existence, the virus activates, comes out of its half-asleep state, kills the host and moves on to another. Generally speaking, in the course of evolution, it was those parasites who are able to combine these two strategies that won. It's like the ability to correctly distribute your bets in a casino. And it is very important to understand that the death of the host or its serious condition is by no means something beneficial for the parasite. This is a side effect of his activities.

Viruses and evolution

The reproduction of viruses, as a rule, does not bode well for individual organisms. Although, on the other hand, viruses can stimulate the immune system. There were even attempts to cure cancer with the help of infection with viruses. But in general, parasites and viruses play a huge role in the course of evolution, without them there was, there is, and there will be no life. And the whole history of life is the history of the joint evolution of the interaction of parasites with the host. And increasing the complexity of protecting hosts, improving the immune system would be impossible without constant interaction with parasites. In particular, it can be shown mathematically that the emergence of multicellular organisms is stimulated in many ways by protection from viruses. Multicellularity becomes advantageous when cells are attacked by a virus: it is advantageous when one cell takes a blow and, using the mechanisms of programmed cell death, can kill itself and rid others of the virus. And many other adaptations that exist in cellular organisms are associated either with protection from viruses, or with the genetic material that the host receives from the virus.

The following example can be given. There is a rather famous enzyme called telomerase – this is the enzyme that ensures the stabilization of our chromosomes, as if making sure that they do not become shorter. This is absolutely necessary for the survival of the body, and the activity of this enzyme is associated with both aging and cancer. And initially, at the dawn of the formation of eukaryotes, this very telomerase was nothing more than a reverse transcriptase, which in early eukaryotes was part of one of the mobile genetic elements. And we must always remember that our own genome consists of about two-thirds or a little less of the remnants of mobile genetic elements. Most people think that this is useless garbage, but there are so many of them that many of them are used for all sorts of needs. Thus, the evolution of hosts is never free of parasites and takes a lot from them.

Evolution and classification of viruses

In 1971, the great American scientist David Baltimore proposed classifying viruses depending on the type of genomic nucleic acid – DNA or RNA. The type of virus, according to this classification, determines the cycle of its reproduction. But in nature, these classes are distributed very unevenly. If we look at what types of viruses infect different organisms, we get an interesting picture. In bacteria and archaea, the vast majority are viruses containing double–stranded DNA. And eukaryotes are significantly dominated by RNA viruses, of which there is simply a fantastic variety. The reasons for these differences are very interesting, but well understood only in a few cases. For example, large DNA-containing viruses cannot spread in plants, they do not survive there and are present only in algae. In higher plants, their place is taken by RNA-containing viruses. This notion of a niche seems to determine the differences in the spread of viruses. But it is not always possible to understand exactly.

Evolution of immunity

It is possible to talk about the evolution of immunity for a very long time, but it is important to understand some very important things. Everyone knows that the replication of genetic material is based on the complementarity of nucleic acids. And, accordingly, important immune systems are also based on this principle. In particular, you can take a piece of RNA, and it is suitable for recognition. This is a powerful weapon against an alien, a parasite, in particular viral genomes. But where to get this unique protective nucleic acid? From the genome of the parasite itself. This can be done in different ways. For example, in eukaryotes, as a rule, the RNA virus genome is cut into small pieces, and then part of these pieces is used to find out a unique place in the parasite genome and destroy it with the help of the nuclease enzyme, which is part of this complex. This is a simple and elegant principle.

However, when the infection passes, this process stops, and vaccination does not occur. And the next step is to ensure vaccination. This is exactly what the CRISPR system does. She pays for it with quite a lot of complexity and the possibility of autoimmune reactions. But nevertheless, it is well adapted to memorize information about the parasite. It includes elements of someone else's genome in its own DNA – this is the basic principle of the functioning of the CRISPR system. And this powerful principle is to use the complementarity of nucleic acids, the same principle of replication, in order to separate someone else from their own and destroy it. This is a method that is used by all organisms. The second way is that the recognition of one's own and someone else's is carried out with the help of specific proteins – this is what our immune system does, using receptors on cells that recognize the virus, and soluble antibodies. In general, the whole path of immunity in the global sense is the recognition of one's own and someone else's, the protection of one's own and the destruction of someone else's. And in the process of evolution, this is done in a huge number of different ways.

In the long term, the complete destruction of viruses is neither necessary nor possible. But the destruction of human diseases that they cause, such as smallpox and polio, is an already existing reality and an understandable goal. These are viruses that are a dead end of evolution and at the same time kill the host – they really can and should be eliminated. There are good vaccines against major viral diseases, with the exception of rapidly changing viruses such as influenza or HIV. In other cases, the vaccines work quite well. A lot of research is being conducted in the field of such rapidly and unpredictably changing viruses. Scientists are trying to figure out how to predict the evolution of these viruses on a micro-scale and get effective vaccines. It is too early to wait for the completion of these works. The big problem is not so much the newly emerging viruses, but the ones coming from different distant places, such as the Zika virus.

About the author:
Evgeny Kunin – PhD, Leading Researcher at the National Center for Biotechnological Information of the National Medical Library of the National Institutes of Health of the USA.

Portal "Eternal youth" http://vechnayamolodost.ru  23.11.2016