What are viruses and how do they function?

16/11/2020

Viruses are small pieces of RNA (ribonucleic acid) or DNA (deoxyribonucleic acid), many are encapsulated in a protein-based envelope known as a capsid, others protect their genetic material with a membrane or envelope derived from the cell they infect and some others also surround their capsid with a cell membrane.

Viruses have evolved to reproduce within the cell they infect, since they are not capable of doing so by themselves because they lack the necessary molecular machinery. Then, there are three problems that a virus must solve in order to make more copies of itself: 1) how to reproduce inside the cell that it infects? 2) how to spread from one host to another? and 3) how to avoid being eliminated by the defenses (immune system) of the host?

Generally speaking, DNA viruses use parts of the host's information, as well as part of its cellular machinery. The problem with this strategy is that most mature host cells are not actively replicating, they are resting to save energy.

Therefore, DNA viruses need to find a way to activate the engine ("powering up") of the host cell or, alternatively, bring in the attachments of those cell parts that are not active when the virus enters. Basically what viruses do to reproduce is hijack the cell's factory to produce viruses instead of new cells.

On the other hand, RNA viruses bring with them their own genetic information copying machines (e.g. RNA-polymerase enzyme) or possess genes (genetic information) that produce the proteins required to assemble the copying machines inside the cell they infect, which makes them independent of the cellular machinery and capable of infecting cells that are not actively reproducing.

The way in which the different types of virus spread is very varied: by air when we breathe, when we ingest them with food, those that we obtain directly from our mothers, those that we obtain through sexual contact and those that are transmitted by insect bites such as mosquitoes.

The skin represents an impenetrable barrier for a virus because it is made up of layers of dead cells, and viruses need living cells to be able to reproduce. Therefore, unless the skin is broken (e.g. wounds) or bitten (e.g. mosquitoes), viruses have chosen to take other routes of entry into the host. For example, by attacking the cellular mucosal barrier that covers the respiratory and reproductive system. Even so, the mucosal barrier is highly effective and helps eliminate most of the viruses that are trapped in it.

The mucosa is helped by macrophages (defense cells) that ingest the viruses and eliminate them. In the case of the vagina, in addition to the mucosa, the bacteria that colonize the reproductive tract produce acid, which makes the environment unfavorable because many viruses are sensitive to acidic conditions. And as if that were not enough, those viruses that decide to enter the digestive system must deal with very aggressive defenses, such is the case of saliva which contains powerful compounds that deactivate the viruses.

In addition, if they manage to pass through the saliva, they are awaited by a bath of stomach acids seasoned with digestive enzymes (designed to break down proteins, carbohydrates and lipids) and bile salts (a detergent to break down ingested fats) that are very effective in breaking down the sheaths that protect the genetic material from viruses.

Finally, once the viruses manage to pass the physical barriers imposed by the skin, they face the innate and adaptive immune system. The innate system is so called because it is a defense system that all animals seem to have. It is made up of four weapons:

1) Phagocytes, which are white cells (e.g. macrophages) that patrol the tissues of the body cleaning it of garbage, cellular debris, and invaders.

2) The complementary system, which is made up of approximately twenty proteins produced in the liver and found in high concentrations in the blood and tissues, these work together to destroy the invaders (they make holes in the protein envelope or cell membrane of the invaders) and to give the alarm signal to other members of the immune system team. This system is very old, even the sea urchins that evolved about 700 million years ago have it.

3) The warning system of interferons, which are proteins produced by the cells that bind to small receptors (keys) on the cell membrane and serve to alert the cell that it will soon be attacked by viruses, in which case the infected cell will commit suicide!

4) Natural killer cells, this type of cells are in charge of destroying all the cells that have been infected by some virus; the mystery is how do they do it? It seems that there are signals at the molecular level, such as interferons, that indicate something like "kill me because I am infected", but there are also signals that say "don't kill me, I am healthy", details are still being discovered.

Usually the innate immune system is good enough at controlling infections, but there are times when this system is not enough, mainly when the amount of virus produced during the initial stages of infection is very high. This is when the adaptive immune system comes into play. This system is made up of two weapons: antibodies and T-killer cells (also known as CTL):

1) antibodies (small molecular tags) are produced on special cells known as B cells. These cells have an enormous diversity of small labels on their surface (cell membrane), which are used to recognize any organic molecule that may exist, such as pathogens.

When B cells encounter an invader (e.g. virus), a chain reaction occurs that causes many B cells to be generated that will produce only the specific tags (antibodies) that were selected by the invader. In this way the antibodies or tags stick to the surface of the invader or infected cells and send a warning message (some tags help prevent viruses from infecting healthy cells by blocking entry into the cells); these messages would be something like: "Hey, I am a cell that is infected, please destroy me" or "Here is a virus, it must be destroyed".

Finally, some B cells become memory cells of the immune system; that is to say, they are the cells that will protect us in case the same invader reaches the body again.

2) T-killer cells or CTL are white cells that, like B cells, have a variety of labels on their surface that are used to analyze the protein fragments that the body's cells expose on their surface. As viruses use the machinery of the infected cell to produce viral proteins, fragments of these are brought to the cell surface and exposed to the outside by special molecules (counters); once there, these are evaluated by the CTL cells and in case of detecting an infection, the T-killer cells will destroy the cell that has been infected.

The way in which viruses evade these host defenses are very varied, some of them as follows:

1) production of proteins that interfere with or disable the cell's molecular warning signals (e.g. blocking the interferon production system), and that can prevent the molecules involved in activating the cell death programming from coming into play; thus, allowing the cell to live long enough until the virus has produced a large number of new viruses that will infect more cells.

2) The adaptive immune system (B cells) has memory for the types of viral strains to which the individual has already been exposed, but the high mutation rates cause the virus to change rapidly so that the adaptive immune system no longer recognizes it and escapes (this method is known as "bait and switch").

3) Some viruses with different origins (e.g. human influenza and avian influenza) can mix their genetic material when they infect the same individual of the same or another species (e.g. pig), this makes the immune system have no memory against this new variant!

4) Using disguises to hide from the cellular defense system; for example, there is a group of viruses known as rotavirus, which have a triple protein layer protecting their genetic material, of which only the outermost is removed by enzymes from the digestive system, but the genetic material is kept hidden from the immune system within the other two sheaths.

5) Hiding from the defense system by taking alternative routes of infection; for example, the hepatitis A virus enters by mouth, but then takes a shortcut to the liver where it reproduces in large quantities. Since the defense system against intestinal invaders is different from that which defends internal organs and blood, it takes a while for the defense system to realize that it has been tricked, and it is that time that the virus uses to reproduce!

6) Fusion of several cells of the host (forming agglutinations known as giant cells) to transmit directly to each other without exposure to the defense system.

7) Destruction of defense cells that regulate the coordination (the coach and the team captain) of the host's immune response, causing that the adequate defense response is not generated.

8) Using decoys to distract the defense system; for example, the Hepatitis B virus produces many viral envelopes without genetic material (empty boxes!), then the defense system recognizes these envelopes by the labels on their surface, but cannot distinguish between those that carry genetic material and those that do not, so many viruses escape!

Assuming that the virus has evaded all defenses, it has two general strategies to enter the interior of the cell it will infect:

1) the proteins on the surface of the virus envelope bind to molecular receptors on the cell membrane, once this is done a door is opened through which the viral genetic material is injected into the cytoplasm of the cell;

2) the proteins of the virus envelope bind to the molecular receptors of the cell membrane, and then the whole virus is encapsulated in special containers made of cell membrane, which are taken inside the cell. Once there the protein envelope of the virus and the container membrane fuse and the genetic material of the virus is released, the virus uses molecular signals to target the cell nucleus so that it can use the cell machinery to make more copies of itself.

GLOSSARY

DNA - deoxyribonucleic acid; is a chemical component that contains genetic instructions used for the development and functioning of organisms, and is transmitted from one generation to another.

RNA - ribonucleic acid; is a chemical component that helps to transmit the genetic information contained in the DNA to the protein factories located in the cytoplasm of the cell.

Antibodies - are proteins produced by white cells of the adaptive immune system that are used to identify and neutralize foreign elements in the body such as bacteria, viruses or other types of parasites.

Capsid - a structure made of proteins that surrounds and protects genetic material from the virus. It may be surrounded by an envelope made of cell membrane.

Carbohydrate - molecules composed of carbon, hydrogen and oxygen that have the main function of being an immediate energy source for living beings, as well as giving structure to the cells.

T cells - belong to the group of white cells or leukocytes known as lymphocytes. They are in charge of coordinating the cellular immune response and eliminating specific foreign elements from the body.

Cytoplasm - is the part of the cell body that is contained between the cell nucleus and the plasma or cell membrane. It is composed of a very fine colloidal or semi-solid substance that serves as a support for various cellular components or machinery (e.g. mitochondria, ribosomes, Golgi apparatus).

Enzyme - a type of protein used to give structure and to help speed up certain chemical reactions.

Phagocytes - are cells present in blood and other animal tissues capable of consuming and eliminating cellular debris and foreign elements such as microorganisms. They are an important part of the innate immune system.

Gene - segment of DNA, which represents a unit of genetic information that allows the synthesis of a specific protein.

Host - a living organism that houses another organism either on the outside or inside. Usually the organism living inside or on the host is harmful, but sometimes it may have no effect at all (commensal) or may be beneficial (mutualistic).

Interferon - proteins produced by the immune system in response to invading agents such as viruses and cancer cells. Its functions are to activate immune cells, interfere with virus replication, signal cells that are infected so that they can be eliminated and increase the resistance capacity of healthy cells to new viral infections.

Lipid - molecules composed of carbon and hydrogen and to a lesser extent oxygen, may contain phosphorus, sulfur and nitrogen. Their main characteristic is that they are not soluble in water, serve as an energy reserve, give structure to the cell membrane and can be hormones that regulate body functions.

Macrophages - cells of the innate immune system that are located in different tissues of the body and are derived from the bone marrow. They are a type of phagocytes, so their function is to eliminate cellular debris and foreign or invasive elements.

Mutation - change in the genetic information of a living being, which produces variations in the protein encoded by a specific gene. A mutation normally has a negative effect on the organism, but sometimes the effect is positive and helps the survival and reproduction of the organism.

Protein - molecules composed of amino acids, which have various functions. They are the structural base of living organisms (our body is made of proteins), they are antibodies that defend us from invaders, they are enzymes that help in the chemical reactions of the body and help maintain a stable chemical environment (pH).

Replication - mechanism that allows the DNA or genetic material to duplicate, that is to generate an identical copy of the information that will be transmitted to the daughter cells.

Cell Membrane Receptor - proteins found on the surface of the cell membrane that allow the interaction of certain substances (hormones, neurotransmitters) with the cell. In other words, they serve as receptors of information from the outside environment and transmit that information to the inside of the cell.

Adaptive Immune System - is made up of cells and mechanisms that defend the host, generating a specialized and specific response against specific parasites. This defense system is only present in vertebrate animals (i.e. those with bones) and can generate long-term immunity. Unlike the innate immune system, its response is slow and it takes the body one to two weeks to build up the specific defenses; however, it is a very efficient system.

Innate Immune System - is made up of the cells and mechanisms that defend the host from infections by other organisms. This defense system is not specific, that is, it will recognize and respond to any element that is foreign to the organism. It is a defense system that is found in both animals and plants. Unlike the adaptive immune system, this system does not confer long-term immunity.

By Diego Santiago Alarcón, Source: Inecol