VIRAL REPLICATION: CHARACTERISTICS, VIRAL REPLICATION CYCLE, EXAMPLE (HIV) - BIOLOGY - 2024

The viral replication is the way the different types of viruses multiply within the cells invading. These DNA or RNA entities have many different strategies for recruiting structures within the cell and using them to produce copies of themselves.

The biological "function" of any type of viral replication is to generate new viral genomes and proteins in sufficient quantities to ensure the spread of the viral genome that invaded the cell.

Steps of viral replication (Source: Alejandro Porto via Wikimedia Commons)

All viruses known to date need cell enzymes for their multiplication, since they do not have their own enzymes that allow them to replicate and reproduce on their own.

Viral molecules are capable of invading virtually any type of cell on the biosphere.

Due to this, humanity has directed a large amount of resources and efforts to understand not only the functioning of viruses, but also viral replication, since this process is key to the proper control of all diseases that are the result of infection of viral origin.

Viruses need to reach the interior of cells and, to do this, they must put in place specialized mechanisms to "circumvent" the endogenous defenses of their hosts. Once inside the "colonizing" individuals, they must be able to enter their cells and replicate their genome and proteins.

characteristics

Viral replication presents important variations in each species of virus; Furthermore, the same species can harbor different serotypes, “quasispecies” and viruses with great modifications in their genomic sequence.

The genome of viruses can be composed of nucleic acids such as DNA, RNA or both, single or double band. Said molecules can also be in a circular, linear shape, such as "hairpins" (hairpin), among others.

As a result of the great variation in the structure of viruses, there is a great diversity of strategies and mechanisms to carry out replication. However, some more or less general steps are shared among all species.

Viral replication cycle

Image source: No machine-readable author provided. Guaguaguagua assumed (based on copyright claims).

Generally, the general viral replication cycle comprises 6 or 7 steps, which are:

1- Adsorption or binding to the cell, 2- Penetration or entry into the cell

3- Genome release

4- Genome replication

5- Assembly

6- Matured

7- Lysis or release by budding

Adsorption or binding to the cell

Viruses currently have in their structure a protein or molecule known as an antireceptor, which binds to one or more macromolecules on the outer membrane of the cell into which they wish to enter. These molecules are generally glycoproteins or lipids.

Glycoproteins or lipids on the outer membrane of the "target" cell are known as receptors, and viruses adhere or covalently bind to these receptors using their protein or anti-receptor molecule.

Penetration or entry into the cell

Once a virus attaches to the outer membrane of the cell through the receptor-antireceptor junction, it can enter the cell through three mechanisms: endocytosis, fusion with the cell membrane, or translocation.

When entry occurs by endocytosis, the cell creates a small cleft in a specific region of the membrane, right where the virus is attached. The cell then forms a kind of vesicle around the viral particle, which is internalized and, once inside, disintegrates, releasing the virus into the cytosol.

Endocytosis is perhaps the most common entry mechanism for viruses, as cells constantly internalize vesicles in response to different internal and external stimuli and for different functional purposes.

Fusion with the cell membrane is a mechanism that can only be carried out by viruses that are enveloped by a protective covering called a capsid. During this process, the components of the capsid fuse with the cell membrane and the interior of the capsid is released into the cytosol.

Translocation has rarely been documented and is not fully understood. However, it is known that the virus adheres to a receptor macromolecule on the surface of the membrane and internalizes itself by intercalating between the components of the cell membrane.

Genome release

This process is the least understood and perhaps the least studied in viral replication. During it, the capsid is removed, exposing the virus genome with its associated nucleoproteins.

It has been hypothesized that the envelope of the virus genome is fused with the endocytosed vesicle. Furthermore, it is thought that this replication step is triggered by some factor internal to the cell such as pH or change in electrolyte concentration, etc.

Replication of the viral genome

The replication processes of the viral genome are highly variable between each species of virus; in fact, viruses are classified into 7 different classes according to the type of nucleic acid that makes up their genome.

As a general rule, most DNA viruses replicate within the nucleus of the cells they invade, while most RNA viruses replicate in the cytosol.

Some single-stranded (single-stranded) DNA viruses penetrate the cell nucleus and serve as "template" strands for the synthesis and multiplication of more single-stranded DNA molecules.

Other double-band RNA viruses synthesize their genome through segments and once all the segments are synthesized, they assemble in the cytosol of the host cell. Some genomes contain in their genome the genetic sequence that has the information to encode an RNA polymerase.

Once that RNA polymerase is translated, the replication of multiple copies of the viral genome begins. This enzyme can generate messenger RNAs to produce the proteins that will give rise to the capsid of the virus and other of its components.

Assembly

Once multiple copies of the virus genome and all the components of the capsid have been synthesized, all of these are directed to a specific site of the cell such as the nucleus or the cytoplasm, where they are assembled as mature viruses.

Many authors do not recognize assembly, maturation and lysis as separate processes in the life cycle of viruses, since many times these processes occur consecutively when the concentration of the parts and the genome of the virus inside the cell it is very high.

Matured

During this phase the virus becomes "infectious"; that is, the capsid proteins mature or conformational changes occur that transform the initial structure into particles capable of infecting other cells.

Some viruses mature their structures inside the cells they infect, others only do so after they cause cell lysis.

Lysis or release by budding

In most viruses, release occurs by lysis or budding. In lysis, the cell breaks down and releases its entire contents into the extracellular environment, allowing assembled and mature viruses to travel freely to find another cell to infect.

Release by budding is specific to viruses that possess a lipid and protein envelope. These pass through the plasma membrane forming a kind of intracellular vesicles.

Example of viral replication (HIV)

Viral replication cycle of the HIV virus. Source: Jmarchn

The Human Immunodeficiency Virus, better known as HIV, is one of the viruses that has caused the highest number of human deaths in the world. It is an RNA virus that directly affects a type of white blood cell called CD4 lymphocytes.

Fixation of the virus is done through the recognition and binding of the virus capsid proteins with the cell membrane proteins of CD4 lymphocytes. Subsequently, the capsid fuse with the cell membrane and the virus content is emptied inside.

In the cytoplasm, RNA is reverse transcribed and forms two DNA bands that are complementary. The double-band DNA molecule integrates into the genome of the host cell, in this case the CD4 lymphocyte.

As part of the genetic information of the cell, DNA of viral origin is transcribed and translated as would any strand of genomic DNA of the lymphocyte.

Once all the components of the virus have been produced in the cytosol, the viral particles are assembled and expelled into the extracellular environment through budding. Several hundred thousand bumps form and, when released, give rise to mature HIV particles.

References

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