Viral Life Cycle

Viruses can only infect a specific set of cells. In order to infect a cell, the virus has to bind to specific receptors on the host cell. Without the proper receptors, a cell is essentially invisible to the virus. Once the virus binds the correct receptor, the virus and the cell are brought into close enough proximity to permit additional interactions. Enveloped viruses fuse with the plasma membrane of a cell, allowing the entry of the virion into the host cell. Sometimes a host cell may misinterpret the binding of a virus to the membrane as nutrients or other useful molecules and will actually bring the virus into the cytoplasm via endocytosis. As mentioned earlier, bacteriophages use tail fibers to anchor themselves to the cell membrane and then inject their viral genome into the host bacterium using the tail sheath. Some tail fibers even have enzymatic activity, allowing for both penetration of the cell wall and the formation of pores in the cell membrane. After infection, translation of viral genetic material must occur in order for the virus to reproduce. This requires translocation of the genetic material to the correct location in the cell. DNA viruses must go to the nucleus in order to be transcribed to mRNA. The mRNA then goes to the cytoplasm, where it is translated to proteins. Genetic material from positive-sense RNA viruses stays in the cytoplasm, where it is directly translated to protein by host cell ribosomes. Negative-sense RNA viruses require synthesis of a complementary RNA strand via RNA replicase, which can then be translated to form proteins.5

DNA formed through reverse transcription in retroviruses also travels to the nucleus, where it can be integrated into the host genome. Using the ribosomes, tRNA, amino acids, and enzymes of the host cell, the viral RNA is translated into protein. Many of these proteins are structural capsid proteins and allow for creation of new virions in the cytoplasm in the host cell. Once the viral genome has been replicated, it can be packaged within the capsid. Note that the viral genome must be returned to its original form before packaging; for example, retroviruses must transcribe new copies of their single-stranded RNA from the DNA that entered the host genome. A single virus may create anywhere from hundreds to many thousands of new virions within a single host cell.5

Viral progeny may be released in multiple ways. First, the viral invasion may initiate cell death, which results in spilling of the viral progeny. Second, the host cell may lyse as a result of being filled with extremely large numbers of virions. Lysis is actually a disadvantage for the virus because the virus can no longer use the cell to carry out its life cycle. Finally, a virus can leave the cell by fusing with its plasma membrane in a process known as extrusion. This process allows for survival of the host cell, and continued use of the host cell by the virus. A virus in this state is said to be in a productive cycle.

Depending on growth conditions and the specific virus, bacteriophages may enter a lytic or lysogenic life cycle. These two phases are similar to the lysis and productive cycle methods of progeny release discussed above.

During a lytic cycle, the bacteriophage makes maximal use of the cell’s machinery with little regard for the survival of the host cell. Once the host is swollen with new virions, the cell lyses, and other bacteria can be infected. Bacteria in the lytic phase are termed virulent.

In the event that the virus does not lyse the bacterium, it may integrate into the host genome as a provirus or prophage, beginning the lysogenic cycle. In this case, the virus will be replicated as the bacterium reproduces because it is now a part of the host’s genome. Although the virus may remain integrated into the host genome indefinitely, environmental factors (radiation, light, or chemicals) will cause the provirus to leave the genome and revert to a lytic cycle at some point. As mentioned earlier, trapping of segments of the bacterial genome can occur when the provirus leaves the genome, which allows transduction of genes from one bacterium to another. Although bacteriophages can kill a host bacterium, there may be some benefit to having them integrated in the lysogenic cycle. Infection with one strain of phage generally makes the bacterium less susceptible to superinfection (simultaneous infection) with other phages.5

lytic-lysogenic-cycle

Retroviruses are enveloped, single-stranded RNA viruses in the family Retroviridae; usually, the virion contains two identical RNA molecules. These viruses carry an enzyme known as reverse transcriptase, which synthesizes DNA from single-stranded RNA. The DNA then integrates into the host cell genome, where it is replicated and transcribed as if it were the host cell’s own DNA. This is a clever mechanism because the integration of the genetic material into the host cell genome allows for the cell to be infected indefinitely, and the only way to cure the infection is to kill the infected cell itself. The human immunodeficiency virus (HIV) is a retrovirus that utilizes this life cycle, which is one of the characteristics that make HIV so difficult to treat.

Transduction is the only genetic recombination process that requires a vector—a virus that carries genetic material from one bacterium to another. Viruses are obligate intracellular pathogens, which means that they cannot reproduce outside of a host cell. Because of this, bacteriophages (viruses that infect bacteria) can accidentally trap a segment of host DNA during assembly. When the bacteriophage infects another bacterium, it can release this trapped DNA into the new host cell. This transferred DNA can then integrate into the genome, giving the new host additional genes.

Prions are infectious proteins and are, thus, also non-living things. Prions cause disease by triggering misfolding of other proteins, usually involving the conversion of a protein from a α-helical structure to a β-pleated sheet. This drastically reduces the solubility of the protein, as well as the ability of the cell to degrade the misfolded protein. Eventually, protein aggregates form, and function of the cell is reduced. Viroids are small plant pathogens consisting of a very short circular single-stranded RNA. Viroids can bind to a large number of RNA sequences and will silence genes in the plant genome. This prevents synthesis of necessary proteins and can subsequently cause metabolic and structural derangements in the plant cell. Viroids are classically thought of as plant pathogens, but a few examples of human viroids do exist, including the hepatitis D virus (HDV). Alone, HDV is innocuous; however, when co-infected with hepatitis B virus (HBV), HDV is able to exert its silencing function on human hepatocytes.

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