Interferon – the basis of antiviral protection of fish, birds, and mammals
Interferon (IFN) is a part of the innate immunity of all vertebrates. The first interferon system appeared in fish. Then it was inherited by amphibians, reptiles, birds, and mammals. With the evolution of animals, their IFN system also evolved. For example, 21 types of interferons have already been found in humans, which differ in their functioning nuances.
The most important biological property of interferon is its antiviral activity. The IFN molecule does not fight directly against the viral particle but triggers all the antiviral protection mechanisms without exception.
Protecting against the virus and destroying it, the body’s cells exchange interferon molecules as signaling messages. When attacked by viral particles, almost any cell in the body can synthesize interferon molecules, informing the rest of the cells that it is infected.
All types of cells in the body can capture the IFN molecule. They capture interferon on their surface with the help of unique proteins called receptors. Interferon receptors are a significant component of the innate immune system.
Tissue cells, having received the IFN signal, rearrange their biochemical processes so that:
- try to protect themselves from a viral attack;
- slow down the reproduction of the virus if the defense failed and the virus got inside.
Immune cells, having received the IFN signal, move in the direction from which the signal came. Thus, at the site of the virus attack, there are many innate immune cells that:
- directly destroy the virus;
- synthesize many interferon molecules (more than tissue cells) to attract other immune cells to the infected area.
Viral attacks are most often directed at the epithelial (external) tissues of the respiratory system, digestive tract, reproductive tract, and mucous membranes of the eyes. Therefore, the density of immune cells in these tissues is high so that many interferon molecules can be quickly synthesized in the event of an attack.
Versatility and responsiveness of the interferons
A critical evolutionary step in developing the vertebrate IFN system is its universality concerning different types of viruses. Interferons work equally effectively in attacks of already known viruses and new viruses in the population.
The main task of the IFN system is to protect the body until the acquired immunity is activated. Acquired (adaptive) immunity is a perfect tool of the body to fight viruses. However, it takes 3 to 5 days to run this high-precision mechanism.
In the first days of the disease, only the interferon system’s work protects the body from the virus’s deadly effects. Within 3 hours after infection, the body’s cells begin to produce IFN molecules.
The evolutionary struggle of viruses with the interferon system
Over millions of years of interspecies warfare, the best surviving virus mutations were those that learned to bypass or slow down interferon effects.
Some viruses can block the synthesis of interferon by cells. This hindrance to the innate immune response gives the virus a significant temporary advantage for unhindered reproduction. This ability was most pronounced during the COVID-19 coronavirus pandemic caused by the SARS-CoV-2 coronavirus. In many patients, coronavirus blocked the production of interferon, as a result of which it affected almost all vital organs and led to death.
Another evolutionary ability of viruses is to block the very action of interferon. For example, the Ebola virus causes an infected cell to produce a unique protein that makes the cell immune to interferon molecules.
The evolutionary struggle of viruses against the interferon system is an endless contest. The immune system finds another effective antiviral solution, and viruses after some time mutate so that this solution is circumvented.
Nevertheless, the man had found a way to gain an advantage in this battle. He learned how to synthesize interferon on an industrial scale and use it when the body’s interferon is not enough to fight the disease.
Some viruses that have strategies for fighting the interferon system:
| Virus family | Representatives |
| Coronaviruses | SARS-CoV (SARS) |
| MERS-CoV (Middle East respiratory syndrome) | |
| Orthomyxoviruses | Flu viruses A, В, С, D |
| Herpesviruses | Herpes simplex virus (HSV-1, HSV-2) |
| Cytomegalovirus | |
| Hepatic Viruses | Hepatitis С, В |
| Retroviruses | Human immunodeficiency virus (HIV-1, HIV-2) |
Antiviral protection mechanisms
1. When the cell receives the IFN signal, it begins to prepare for the virus’s invasion. Under the influence of interferon, the activity of about 1,000 genes in the cell changes.
Some genes stop working, and the synthesis of proteins associated with them stops. That makes the cell worse – it stops growing and multiplying. However, in the case of infection, such a mechanism allows you to slow down the virus’s reproduction since the cell resources are used to synthesize new viral particles.
On the contrary, other genes are activated by interferon, and the cell begins to produce antiviral defense proteins. Some proteins directly fight the virus – they seek to suppress the virus at each stage of its life cycle. Another group of synthesized proteins spreads information about the virus invasion throughout the body and coordinates antiviral defense. This group also includes interferon.
All genes activated in the cell under the influence of interferon are called interferon-stimulated genes (ISG). Their activation is critical to prevent a hyperinflammatory immune response, leading to significant damage to the body’s tissues and death.
2. Interferon triggers another mechanism of antiviral defense – it activates several types of cells of the immune system that can absorb and digest foreign particles. These immune cells are called phagocytes. They, like interferon, are part of the innate immune system.
Following the signals of the IFN, phagocytes find the site of the virus attack and seek to destroy foreign particles and infected cells. Interferon also stimulates phagocytes to intensively produce reactive oxygen species, which are needed to digest foreign microorganisms.
IFN contributes to the infected cells became more visible to the phagocytes. In this case, the phagocyte will quickly find the infected cell and destroy it along with new viral particles that did not have time to leave it.
3. Another mechanism of interferon in antiviral defense is to help the acquired immunity. Acquired immunity is the most effective evolutionary tool for protecting against infections. Acquired immunity is a set of highly specialized cells and proteins that specifically destroy the pathogen of infection and do not damage the body’s tissues. The acquired immune system is responsible for long-term immune memory and does not allow the disease to develop during a repeated encounter with the infection. Interferons contribute to the maturation and learning of the cells of the acquired immune system. IFN promotes the activity of cells that produce specific markers of a foreign gene. These markers are called antibodies.
4. The IFN system has an important feature that has become another mechanism of antiviral protection. If the body is already infected with a virus, it becomes much more difficult to infect it with another virus type. This mechanism, scientists called the interference of viruses (interference, English. – interference, interference, obstacle, mutual influence).
The evolution of knowledge about viruses and interferons interference
Virus interference was discovered in 1937 by English virologists George Findlay and Frederick McCallum.
In one experiment, scientists injected laboratory monkeys with a deadly virus, but the monkeys survived – they did not even develop the disease. Scientists began to closely study this phenomenon, trying to understand what protected the animals from the deadly virus.
Comparing the facts, the scientists found that a few days before the lethal injection, the same monkeys were injected with a weakened yellow fever virus.
The experiment was repeated many times with the same result. This experiment was the first in the discovery of a new mechanism of antiviral protection.
It was not possible to explain the mechanism of virus interference at that time – there were no methods for studying individual living cells’ processes. A working hypothesis explaining the new phenomenon was the competition between different types of viruses for nutritional resources.
10 years later, in 1947, the American virologist John Franklin developed a method for growing plant and animal cells under artificial conditions (in vitro, lat. – in glass; in vitro, English-artificial). This development allowed us to study how cells live and interact with the external environment.
In another 10 years, 1957, the English scientist Alik Isaacs and the Swiss Jean Lindenman discovered a protein molecule that cells synthesize in response to a viral attack. Scientists have proved that the appearance of these molecules explains the phenomenon of virus interference.
Isaacs and Lindenman used Franklin’s artificial cell culture technology to observe the process of infecting cells with viruses.
First, one type of virus was added to the cell culture. After some time, another kind of virus was also added there. There were many healthy cells, so the researchers expected to see that different viruses did not compete strongly for food resources in the form of healthy cells. Scientists sought to see a less vivid phenomenon of virus interference.
The reality was the opposite-the virus that was added second could not infect healthy cells. Nevertheless, a new protein substance appeared in the environment, which the cells produced in response to introducing the first virus. Moreover, this protein was not present in healthy cells. The discovered protein substance was called interferon (IFN).
Thus began the era of studying a new mechanism of antiviral protection of vertebrates.
Actual knowledge about human interferon.