Viruses are not always enemies

2018/03/01 Etxebeste Aduriz, Egoitz - Elhuyar Zientzia Iturria: Elhuyar aldizkaria

They are very small and very simple, with very little genetic information, but they are able to do amazing things and not always for evil. They have been important stimuli of evolution, and in many cases we are discovering that it provides the guest with certain capacities and benefits. In these times, thanks to new technologies, we are better aware of viruses, it seems that we owe them much more than diseases.
Inflammation. ED. : Cynthia Goldsmith, Brian W.J. Mahy, Luanne H. Elliott/Uscdcp.

“A piece of nucleic acid surrounded by bad news,” this is how the virus was defined by Nobel Prize winner Peter Medawar. It is not the most concrete definition, but it is a good example of our vision of viruses, or what we have had for many years. “At first glance we don’t see them very well: they produce diseases, some very serious, 15% of cancers can be caused by viruses, etc.”, explains the microbiologist of the University of Navarra, Ignacio Lopez-Goñi. “But as you dig deeper into the world of viruses you realize that it is an exciting world. Viruses are probably much better than we think.”

“It must be thought that there is a large number of viruses in the world, it is calculated around 10 31 and that of those millions and millions only a few are pathogens,” explains Miren Basaras Ibarzabal, microbiologist of the UPV. “Therefore, many can be hypothetically beneficial. But we still do not know what the majority do.”

It is becoming increasingly clear that viruses have played an important role in the evolution of life. In fact, “viruses are systems capable of exchanging genetic information between cells,” says Lopez-Goñi. “Many times it is discussed whether viruses are living beings and I don’t know how to respond to it either, but surely from the first moments of the genesis of life there were viruses there and have served to increase genetic diversity. Viruses are the engine of evolution.”

Focus on evolution

There are many indications of this in our genome. The genome is plagued by viral sequences called endogenous retroviruses. They are considered to be fragments of DNA from those who have been viruses. Thus, 8% of our genome could come from virus. In general, they have already lost the ability to create viruses, but they can have many other functions. Some offer resistance to other viruses and many others are regulators of our genes.

More and more data show that it is possible that a virus of this type has allowed to develop the lime so important for mammals. When the embryo is installed in the uterus, some cells of the embryo begin to form lime. Among these cells, those that directly touch the uterus produce a protein called syncytin. It is essential for the correct development of the relationship or border between the tissues of the mother and those of the embryo. Because the cytin gene is almost equal to the env gene of viruses. Viruses use the protein that encodes this gene to fuse the host cell with the membrane.

Fagos attacking a bacterium. ED. : Graham Beards/CC-BY-SA.

Recently, another study has shown that this type of endogenous retrovirus can also be key in the evolution of the immune system. And similar examples are being drawn constantly. For example, at the beginning of the year, two research groups published that some of the microbes used to send information from the neuron to the neuron are actually very similar to viruses. These microbes, which carry inside the protein Arc, have been able to verify that in the mouse are generated connections between neurons that affect the memory in the long term. Well, the Arc gene is very similar to the gag gene used by viruses to form the capside.

Virus Friends Friends Virus

It is partly clear that we are thanks to viruses. “We are also seeing that viruses directly confer certain capabilities to the host. For example, in bacteria we have known for a long time that certain toxins are produced by viruses. And there are similar examples in plants and animals,” explains Lopez-Goñi.

Ignacio López Goñi. Professor of microbiology and virology at the University of Navarra and author of the microBIO blog.

Few plants are able to grow in the warm lands surrounding the geisers of Yellowstone. On the contrary, the herb dichanthelium lanuginosum is common in these areas. This herb is colonized by a fungus while being infected by a virus. Because the symbiosis between the three is essential for the grass to live on lands close to 50ºC. And by creating symbiosis between this virus infected fungus and tomatoes and other plants in the laboratory, they have seen that they acquire the capacity to live in very hot lands (up to 60ºC).

Even one of the biggest enemies of our apple trees, the fragile phylum (the Dysaphis plant), is accompanied by a virus. By infecting viruses, lice develop the wings. The winged lice are smaller and have less fecundity than those not infected, but greater expansion capacity. The virus passes from one site to another through the plant. Unable to reproduce in plant cells, there will be very few viruses in the plant and the wingless lice will multiply at full speed. As it increases, however, it increases the possibility of infecting lice with viruses in the plant. Thus, when there are too many cloths in the plant, the winged lice that can go in search of another branch or plant will be created again.

Microbiome also virus virus

Humans also have a lot of virus. Our bowels, for example, are full of viruses. “The microbiome is researching a lot and we know that bacteria have an important role, but it seems that in this microbiome viroma is also very important,” explained Basaras. “For example, it has been seen that if the balance of viroma is lost, intestinal inflammatory diseases appear.”

Look at Basaras Ibarzabal. Professor of Microbiology at the University of the Basque Country.

Many of the viruses we have in the intestine are phages, bacteriophages, bacteria viruses, and it is possible that they contribute to regulate the populations of intestinal bacteria, as well as regulating some genes of bacteria important for our digestion. “It has also been seen that some phages can modulate or stimulate the immune response, for example, helping to create antibodies,” explains Basaras.

In addition to the intestines, in general, the mucous of the body are very rich in phages. In our dental mucosa, for example, there are 40 times more viruses than in the skin of the dentures. It is the first line of defense against invasive bacteria in the nasal mucosa, mouth, eyes, the entire digestive tract and even lung. The tissues of human lung grew in the laboratory and saw that in this defensive line the viruses are essential. The normal tissue, and the tissue that had silenced the genes to form the mucosa (without mucous membranes), grew and when adding the bacteria observed that the cells of both tissues died the same, that the mucosa did nothing. Subsequently, antibacterial phages were introduced before the bacteria, in which case the advantage of the mucosa was enormous. In addition, they have seen that fagos contain molecules such as antibodies to grasp the mucosal molecules. This suggests a coevolution of mucosa and fagos.

The mucous membranes are very frequent in the animals and in the mucous of all the animal species analyzed, large amounts of fagos have been found. They are a good example of symbiosis between animals and viruses.

More than Fagos

But it seems that, in addition to phages, other viruses can also provide benefits. In the mouse, it has been observed that when intestinal bacteria are damaged (by taking antibiotics, for example), noroviruses fulfill their beneficial functions, contributing, among other things, to the maintenance of the normal structure of the intestine and the immune system. In the mouse it has also been observed that some viruses help to combat other pathogens. Herpesvirus gamma increases resistance to bacteria Listeria monocytogenes and Yersinia pestis. And the NK lymphocytes, very important in the immune system, thanks to the virus latent herpesvirus, acquire the cells infected by virus and the toxic weapons used to kill tumor cells.

Canned mammals are almost the same gene that viruses use to fuse with the host membrane. Thanks to this gene we produce lime. ED. : Fred Murphy, Sylvia Whitefield/USCDCP.

On the other hand, the effects of coinfections can be interesting, as Lopez-Goñi explained: “When you sometimes have a virus infection, a second virus can make things worse, but also vice versa. Some viruses can protect themselves from infections with other viruses, acting on the immune system.”

Although GBV-C slightly slows down the immune system, it does not cause disease. On the contrary, it can be an advantage as it also significantly slows down HIV infection. And although there is less data, it seems that it also happens in the case of Ebola. “This kind of issue has to be learned little by little,” says López.

We have learned with bacteria, although many are pathogenic, many others are beneficial and even essential to our health. And it seems that we take the same path with viruses, even if it is slower. “The bacteria are easier to investigate, so they have been much more investigated. The main problem is the difficulty in detecting viruses. All bacteria have a favorable area in the genome for easy detection with sequencing techniques: Zone 16S RNA. There is no virus. It has improved a lot, diagnostic techniques have been developed a lot, but it is necessary to deepen more. We know more and more, but we lack a lot.”

“This is changing a lot in recent years, and with the new technologies we have, viruses are taking the leading role they have not had so far,” explains Lopez-Goñi. There is much to investigate and discover. But, as Basaras says, “we must think that we are composed of several microorganisms, bacteria and viruses, and that all have a role.” Yes, it seems that we are also viruses.

Domestication of viruses
Viruses, due to their intrinsic characteristics, are very interesting for various uses. For example, phages could be a good treatment for bacterial infections. It’s not something new: a hundred years ago, Félix D’Herell, who gave name to the victims, used them to heal dysentery and anger. And phagotherapy was widely used in the 1930s. But then the antibiotics appeared and with their success the fagos were forgotten, except in the area of Russia. “Now, seeing that there are problems with antibiotic resistance, important groups have begun to investigate in the US, Canada, etc.”, explains Miren Basaras. “Fagotherapy has many problems and limitations, but there is an interesting research route,” says Ignacio Lopez-Goñi. “In addition to the direct use of phages, we can investigate how they act against bacteria.”
The transformation of viruses for our needs is also relatively simple. “Viruses naturally introduce genetic information into a cell. We can manipulate that information to put what we want,” says Lopez-Goñi. This is the case of the genetic transformation of organisms, the creation of induced stem cells, the editing of the genome by means of the CRISPR technique and the geneterapia in general. “For geneterapia similar to adenobirus are used for their characteristics. There are many research that is being carried out to correct defective genes through viruses. In the US there are already protocols approved to treat hemophilia and the results that are being obtained are encouraging,” explained Basaras.
Herpes simplex virus. These viruses are some of those that are testing against tumors. ED. : Fred Murphy, Sylvia Whitefield/USCDCP.
And in the fight against tumors there is more and more evidence with virus. Oncolytic viruses can know the tumor cells and destroy them directly. Or they can be used to help the immune system fight the tumor. “It is being tested with cancers that respond poorly to other treatments. There is a lot to investigate, but it is a rather illusionary path,” says López.
They can also be useful in nanotechnology. For example, you can take advantage of the virus self-assembly capacity to create nanostructures. “Kapside proteins come together spontaneously to form structures as stable as possible,” explains López-Goñi. Thus, the tobacco mosaic virus is used in the construction of nanotubes. And in this sense, the transformation of virus can also generate new materials. In addition, “many of the viruses can learn from the organization of elements to form stable structures — adds Lopez-Goñi — for applications such as nanotechnology, design or even architecture.”