Viral Replication

The central dogma holds that there is a strict flow of information from DNA to RNA to protein. In normal cells DNA sequences are inherited from parent cells and are preserved. Said differently, information never flows in the reverse order; RNA sequences do not get translated into DNA. Protein structure does not lead to RNA or DNA information.

Viruses have developed very powerful, and very disruptive, strategies for circumventing the central dogma. Every known virus is primarily a device that delivers a genetic message to the cell that it infects. Virus "particles" do not possess the cellular machinery described above, and for that reason are not "living" particles. At the same time, the genetic information carried by the virus contains the instructions necessary to convert, more accurately to subvert, the normal cell processes into a focussed set of activities that lead to the production of more virus particles.

Virus infections thus take over living cells, using them to produce new virus particles. This form of "growth" or replication is strikingly different from that of living cells. In normal growth, a single living cell commonly gives rise to two cells as it undergoes cell division. In the growth of viruses, a single virus infects a cell and the infectious process produces many, typically a hundred or more, new viruses. Given the "amplification" of viruses from one, to a hundred, to thousands in just two or three generations, it is easy to see why viral infections can move swiftly within an organism, or between organisms.

Virtually all viruses go through eight key steps in their reproductive cycle:

1. The virus attaches itself to a host cell. A virus uses particular proteins present on its protective coat to attach to a receptor site (a protein or other component located on the cell surface). In most cases, viruses can attach only to a receptor present on a single kind of cell, usually within a limited number of species - such as a human liver cell or white blood cell.

2. The virus (or at least its genetic information) penetrates the plasma membrane and enters the cell. This can occur in several ways. Many viruses enter the cell during the normal process of intracelluar communication. When a cell buds inward to sample the outside environment, the virus is carried in along with it. Viruses with a protective lipid coat (like Hepatitis C), can simply merge their lipid coat with the cell's outer membrane, and fuse to it. As the virus's lipid coat becomes part of the cell wall, the core of the virus suddenly finds itself

An HIV virus attaching to a host cell

Coronaviruses being absorbed into a host cell. The plasma membrane is budding inward, and will release the viruses inside the cell

Hepatitis A virus reproducing inside a cell

Electron micrograph of a respiratory syncytial virus (RSV) in in the process of budding at the cell membrane

A liver cell killed by infection with the hepatitis C virus

inside the cell. Others, like the primitive bacteriophage, forcibly pierce the cell membrane and inject their DNA into the cell.

3. The DNA or RNA of the virus sheds its protective coating to give it access to the cell. In some cases this is accomplished during penetration of the cell membrane (it is injected

directly, or broken open when it is released into the cytoplasm). More often, special enzymes present in the cell are used to dissolve the casing.

4. The virus takes control of cell functions to faciliate its reproduction. The virus's genetic information begins to be read out by the cell, which is now tricked into following the instructions of the viral genes rather than its own. The normal cellular mechanisms are used for copying the viral DNA, making mRNA from viral DNA, and translating viral mRNA into protein. The virus optimizes the cell environment for reproduction - in many cases, it shuts down the other functions of the cell to conserve energy for the production of viruses, and coopts the cell's "factories", the ribosomes, for viral production.

5. The viral DNA or RNA is then copied thousands of times, making the genetic material for new viruses. DNA viruses accomplish this by using the mechanisms of the cell to produce nucleotides (the building blocks of DNA). The DNA strands are then directly copied from the original viral DNA. In some cases, viruses actually dissolve the host cell's genes so that it can be reused in the creation of viral DNA. RNA viruses have a somewhat different strategy for copying their genetic material, which will be discussed in a later section.

6. The virus then uses the cell's ribosomes to create the proteins and capsomeres to create the capsomeres for the virus's capsid (the virus's protective protein shell) and any other needed components.

7. The capsomeres self-assemble around the viral DNA or RNA into complete viral particles.

8. The newly formed viruses are released from the cell into the outside environment. Viruses have evolved several different strategies for departing their host cells. Some viruses simply wear the cell out, escaping the dying cell as it disintegrates. A few synthesize proteins that dissolve the cell to faciliate their escape. Lipid-coated viruses (like Hepatitis C) travel to the inside portion of the plasma membrane and attach to it, creating a bud. The plasma membrane encircles the virus and then releases it inside a bubble of lipid membrane, providing the virus with its protective lipid coat. This process continues for hours at the cell surface until the cell dies from exhaustion.

Once they have escaped the host cell, the newly created viruses infect new cells, endlessly repeating this process - each time creating thousands of new viruses and causing disease, or even death, in their hosts.