Peaceful virus

Nucleic acid and the protein shell that encloses it – this is what viruses are. One might think something with such a simple structure should have the humblest role in nature, yet it is not true. Thanks to their properties, viruses play an important role in regulation of evolutionary processes and help scientists study the world.  

‘The evolutionary strategy of viruses is to constantly reproduce themselves and to stay within the population of the host. Just like other organisms, they participate in natural selection: they mutate and infect new hosts. For example, after a cell has been infected by the influenza virus, hundreds of new virions bud out of it. Among those only the virions with neither deleterious nor favourable mutations can infect new cells. Other virions will die with time,’ said Aleksei Potekhin, Professor in the Department of Microbiology at St Petersburg University.

Aleksei Potekhin

According to Aleksei Potekhin, almost every living creature on Earth has viruses. Realising their evolutionary programme, they function as a natural mechanism for controlling the populations of their hosts. As soon as some species becomes overpopulated, it gets attacked by virus diseases and its number declines. This leads to the appearance of a free ecological niche that will be occupied by another species, and then the cycle will repeat itself. ‘This process is called succession. It is an irreversible natural replacement of one dominant species of the biotope by another one. The most illustrative example is water blooming, which is caused by an excessive algae growth in reservoirs. For example, during the period of blooming of blue-green algae, water in the Gulf of Finland acquires a typical green colour and ill odour. However, in a few days it becomes transparent again, and the familiar view of the gulf is restored. Why does it happen? The reason is viruses that destroy dominant microorganisms. They act under the principle “kill the winner”’ said Aleksei Potekhin.

Another important function of viruses is keeping food chains at the various levels of the biosphere. At the lower level of food chains there are autotrophic organisms that process chemical elements required for cell building (nitrogen, organic hydrogen, phosphor and others) by means of photosynthesis and chemosynthesis. Autotrophs are food of heterotrophs – organisms that are unable to synthesise molecules required for cell building. In the environment, substances necessary for autotrophs appear due to the demise of different species. This is how the circuit of energy and substance is formed. Every element is important in this process. According to the researcher, viruses support the pool of organic substances in trophic chains by regulating the population of their hosts. The hosts die, decomposer organisms transform them into organic substances, which in turn are food for autotrophs. So, the food chain keeps functioning.

Gene postmen

Viruses play a key role in horizontal gene transfer. This is an exchange of genetic information between organisms which is a main mechanism of evolution and provides biological diversity of species. ‘It was long believed that movement of genetic material from one species to another in the absence of kinship between them happens very rarely. However, with time people learned to identify nucleic acid sequences in the genes, and it turned out that horizontal gene transfer takes up a huge share in diversity of genomes,’ says Professor Potekhin. ‘Viruses help to implement horizontal transfer of genetic information by transporting genes from one host to another. For example, viruses take part in gene exchange between bacteria. A bacterial DNA gets into an infectious entity. While a virus is inserting in a cell of another bacterium, it builds itself into a new genome. And then the following scenarios are possible: either the bacterium “gets infected” and dies, or it acquires useful properties and occupies new ecological niches.’ In this way cholera vibrio, which originally had been a nonsymbiotic water bacterium incapable of causing human disease, developed harmful properties.

It is interesting that horizontal gene transfer affected people as well.  For example, up to 8% of the human genome consist of genetic information that was brought there by human retroviruses. These are representatives of one of the numerous virus families, which also includes HIV. These viral genes are not able to cause infectious diseases. Most probably they have some important missions. They participate in regulating chromatin structure and gene expression (the process by which information encoded in a gene is converted into protein existing or acting in cells). Otherwise humans would have destroyed virus sequences in the course of evolution.

‘Retroviruses are structurally very similar to one of the retrotransposons. These are mobile genetic elements that can move from one location of genome to another and invade new genomes,’ points out Tatiana Matveeva, Professor in the Department of Genetics and Biotechnology at St Petersburg University. ‘The line between retroviruses and retrotransposons is quite blurred. The main difference is that viruses are infectious, while transposons are not. Retrotransposons are the most frequent consequences in genome, which account for up to 90% of genomes of some plants.’   

Tatiana Matveeva

Apart from this, viruses exist in humans as part of microflora. Rhinoviruses that cause running nose and some adenoviruses that hide in nasopharynx are usual companions of humans. ‘They keep our immune system on its toes. As a rule, reaction of human organism towards infectious diseases results in victory and given the immune system is all right, infections do not cause severe complications,’ Aleksei Potekhin explains. ‘This is because the human immune system regularly contacts with different viruses which circulate among people or exist inside the human body. Therefore, the immune system trains and learns to fight back. The result of such trainings is the fact that the immune system reacts properly to a new virus threat, it is always prepared for a fight.’

Fair deal

In nature there are examples of viruses protecting their hosts from enemies. For example, prophage (genome of a virus that integrated into a bacterial DNA) in bacteria Hamiltonella defensa that lives in symbiosis with aphids helps them to protect themselves from ichneumon flies (an insect parasite affined to wasps). According to Professor Potekhin, ichneumon flies use other insects for reproduction, for example aphids. They lay eggs in the bodies of aphids, and the eggs feed on their host insects. As a result, new species develop from eggs, whereas the host aphids die. However, it cannot happen if in the aphid’s organism there are bacteria Hamiltonella containing a genome of a toxin dangerous for ichneumon flies. When ichneumon flies’ eggs penetrate the aphid’s body, symbiotic bacteria protect the host by emitting the toxin. Eggs die, aphids stay alive.  

Another example of symbiotic relations is the contrasting colouring of Tulips Rembrandt. Tulips acquired their vivid colour thanks to the Tulip breaking virus. According to Professor Tatiana Matveeva, such a bright colour of the petals attracts a huge number of pollinator insects and makes up for the disadvantages of the virus infection. ‘The decorative effect of these tulips has been highly appreciated in Holland since the 17^th century, the Golden Age of Dutch Painting. Probably hence the name of the tulip,’ says the researcher. ‘Anyway, a few types of tulip have been infected by the virus for several centuries. Only recently Dutch plant breeders have created a breed with the same colouring but not infected by the Tulip breaking virus.’

Right vectors

Viruses are of a great interest for science. They are used in studying structure and functions of cells, as well as in molecular biology, genetics and gene engineering. In a molecule of a virus similar processes go on as in a host cell. Viruses are therefore a simpler and easier model for studying fundamental processes, for example structures of DNA and RNA. ‘Viruses spurred on development of the methods of analysis (electron microscopy and ultracentrifuges), along with an understanding of the molecular basis of life,’ says Tatiana Matveeva. ‘It is thanks to the viruses that the universal triple-nucleotide of the genetic code was discovered. It was proved that a single amino acid in polypeptide is encoded by three nucleotides of DNA and rRNA (or mRNA – messenger RNA).  E. Coli virus Fag Lambda, whose genome was one of the first to be sequenced, has been used for calculating molecular weight of DNA fragments.’       

According to Aleksei Potekhin, virus is a very convenient tool – vector (nucleic acid molecule used in genetic engineering for inserting of genetic material inside a cell). It helps to get to the cell genome, ‘switch off’ some genes, find out which process ceased to function normally, and so discover what those genes were responsible for. The same possibility can be used the other way round: scientists can replace ‘broken’ genes (the ones that have unfavourable mutations) with the correct ones and restore their functions.  

‘Viruses are very effective natural vectors. On the basis of viral genomes of both DNA and RNA viruses, scientists have received vectors for delivering genes to the cells of bacteria, animals, plants and for producing the necessary proteins in them. Viral vectors played an essential role in realising the “Human genome” project and also in creating genomic libraries, whose labelled sequences help decipher unknown genomes of other species,’ points out Tatiana Rogoza, Assistant  Professor in the Department of Genetics and Biotechnology at St Petersburg University.

Tatiana Rogoza

According to Tatiana Rogoza, one of the most important fields of application of viruses is gene therapy. For example, adeno-associated virus vectors are used in treating cancer. ‘Such vectors are almost perfect,’ she says. ‘They do not initiate immune response and have a range of anti-gene structures, different in tissue-specific properties (depending on tissues of a particular organism). That is why they are used as cancer cells growth inhibitors. They block the blood vessels that support a tumour, suppress activity of cancer genes, and are used in suicide therapy, in which cell suicide inducing transgenes are introduced into the tumour.’

Battle with yourself

Viruses are used for vaccine production. As Tatiana Rogoza said, one of the most promising is baculovirus expression system, where baculovirus vector and insect cells are used. It is with the help of baculovirus expression system that multimer antivirus vaccines are produced. They contain virus proteins and do not contain genetic material. An example of such a vaccine is Flublok. It contains two Influenza A hemagglutinin proteins and one Influenza B hemagglutinin.

‘Another way to create a vaccine is to use the virus that will be similar to pathogenic viruses but will not be able to cause infectious diseases. This is how a smallpox vaccine was produced,’ Aleksei Potekhin says. ‘Also, it is possible to synthesise parts of the infectious agent. For example, Hepatitis B vaccine contains one of the proteins of the virus shell, which grows in yeast cells in the absence of the virus. Although this protein itself cannot cause hepatitis, it can trigger an immune response that leads to the development of immunity.’

According to Tatiana Matveeva, we think that viruses are simply sources of infections of humans, animals and plants. However, their role in nature is much more important. For example, thanks to viruses there is such a big variety of species living in harmony, and scientists have the possibility to study the world at the micro and macro levels. Probably, if it were not for the crises that viruses create, science and medicine would not have reached the current level. Many populations would not have acquired qualities necessary for surviving in the face of natural selection.