A. The Viral Invader
Viruses have an enormous impact on human beings and, like bacteria, have been part of our lives since at least the beginning of recorded time. A bas relief from 1500 B.C. Egypt depicts a priest with a shriveled leg, suggestive of a prior infection with polio virus. A thirteenth-century manuscript shows a dog, mouth foaming, attacking a terrified man destined to die from the rabies virus transmitted from a bite. Smallpox is believed to have helped a small band of Spaniards under Cortés subdue the vast and powerful Aztec nation.
As perpetrators of disease, viruses have been viewed as one of the “bad guys” of the microbial world. Variously termed “pirates of the cell,” “viral hitchhikers,” “cellular hijackers,” and “pieces of bad news wrapped up in protein,” these tiny microbes have been perceived as having evil intent. In reality, viruses are just simple microbes, genetic material (that is, nucleic acid) surrounded by protein.
A virus is not a cell. It cannot maintain the characteristics of life on its own. Lacking the biochemical and structural components (cellular machinery) that enable an organism to carry out the life processes—they have, no nuclei, no mitochondria, and thus no capacity to take up and utilize nutrients—they cannot reproduce, metabolize, or conduct any of the basic processes of life on their own.
A virus cannot replicate outside a cell but must seek out an environment that provides not only the nutrients it needs to carry out life processes but also the cellular machinery required for these processes—that is, the environment of a cell. Viruses can infect cells in every kind of organism, including bacteria, plants, fungi, and animals. Viruses show specificity for the organisms and cell types they infect. That is, a specific type of virus will infect only certain organisms and only certain kinds of cells within that organism.
Much smaller than any cell, a typical virus comprises a protein “coat” surrounding its viral genetic material, which can be single-stranded DNA, double-stranded DNA, single-stranded RNA, or double-stranded RNA.
This genetic material contains specific instructions for making the proteins and nucleic acid the virus needs to reproduce identical copies of itself. The proteins encoded by the viral genes must be able to take over the cellular machinery of the cell; this “commandeered machinery” is then used to aid the reproduction of the virus and, in many cases, is no longer available for the growth and reproduction of the infected cell.
Viruses show great diversity in structure, mode of transmission (see Table 3), and manner in which they “hijack” a cell. Unlike bacteria and parasites, whose genomes are double-stranded DNA (dsDNA), viruses can differ in the nature of their genetic material. Some viruses store information in dsDNA. Other viruses have single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), or single-stranded RNA (ssRNA) as their genetic material (see Table 3).
B. The viral way of life
When genetic information is encoded in double-stranded DNA, the enzyme RNA polymerase copies the information from DNA into messenger RNA, which then directs the synthesis of proteins that are responsible for traits of an organism. This flow of information, DNA —> RNA —> protein, is often referred to as the “central dogma.” Because viruses use the host cell’s translational machinery to make viral proteins, they too must use mRNAs to guide the production of proteins. Viruses containing dsDNA will use the host RNA polymerase to produce mRNA (Figure 1 category I).
What happens when information is stored in ssDNA or in ssRNA or dsRNA? When the viral genome is ssDNA, a viral enzyme (or polymerase) must first synthesize a complementary strand of DNA to produce dsDNA from which mRNA is generated (Figure 3 category II). When the viral genome is dsRNA, mRNA is produced by a viral RNA polymerase that the virus carries into the cell (Figure 3 category III).
Viruses with ssRNA can be one of three types:
- positive-strand ssRNA (+ssRNA) viruses in which the viral genome serves directly as mRNA for protein synthesis (Figure 1 category IV). Additionally, the + ssRNA genome serves as a template for producing a negative-strand ssRNA (-ssRNA) via the viral RNA polymerase. The resulting - ssRNA then serves as a template for the production of more + ssRNA again via the viral RNA polymerase. These new + ssRNA can serve as mRNA and also will be encapsulated as the genome of the progeny virus.
- negative-strand ssRNA (-ssRNA) viruses in which the RNA genome is copied into mRNA for protein synthesis by the viral RNA polymerase (Figure 1 category V). Additionally, the - ssRNA serves as a template for synthesis of a +ssRNA via the viral RNA polymerase. The resulting +ssRNA then itself serves as a template for production of more - ssRNA, again via the viral RNA polymerase. These - ssRNA genomes can again be copied to mRNA by the viral RNA polymerase or encapsulated as the genome for the progeny virus.
- negative-strand ssRNA-reverse transcriptase (-ssRNA-RT) viruses in which a double stranded DNA is synthesized from the viral RNA strand by the enzyme reverse transcriptase. This double stranded DNA molecule is then inserted into the host DNA where it is transcribed into mRNA (Figure 1 category VI)
See Table 3 for examples of viruses with the different types of nucleic acids.
The ways different viruses invade and take over a cell varies to some degree but all demonstrate a common pattern. A virus enters the cell and, using different mechanisms depending on the kind of virus it is, takes over the cellular protein synthesis machinery to generate the proteins it needs for itself to reproduce. Like an unwanted guest who eats everything in the refrigerator, uses every clean towel in the house, and on leaving reduces your house to a pile of rubble, the virus utilizes the building blocks and energy stored that the cell has generated for its own growth and reproduction.
The cell is depleted of the materials and energy it needs to repair the damage. The machinery the cell needs to make more of itself is no longer under its control. As a result, the cell often dies from this invasion. A virus may exit a cell by simply lysing (blowing up) the cell or by budding from the cell, picking up some host membrane as it exists. As you will see in the measles and Ebola viruses, a virus that buds from a cell rather than exploding the cell can spread throughout the body efficiently by traveling in infected cells.
Table 3. Examples of viruses