At this point, you should be fairly comfortable with the basic concepts of cell biology. The purpose of this chapter is to build on that basic knowledge and put it together into more complex systems. In addition, we will introduce some more advanced variations on some of the mechanisms and structures that were discussed in earlier chapters. The three topics, viruses, cancer, and immunity, are not only relevant as current news topics, but relate to one another through multiple pathways, which is why they are lumped together.
Though a virus has both genetic material and protein components, it is not a living organism. It does not contain the capability of self-replication, and is completely reliant on the cellular biochemistry of whatever host cell it has infected. The minimal definition of a virus is a nucleic acid genome inside of a protein shell, or capsid. There are variations of this, such as virions (infectious viral unit) that have a membrane coat outside of the capsid, or some that have enzymes inside of the capsid alongside the genome.
Viroids are also infectious non-living particles, but they are only genetic material, RNA, and have no protein capsid. To date, they are only known to infect plant hosts, and apparently spread by direct or extremely close contact with an infected plant. These infectious pathogenic RNA molecules are single-stranded and circular, and relatively small, roughly 200-400 nucleotides.
Again, none of these viral variations are able to fully replicate without cellular machinery. The cells that viruses can infect range across most living organisms. There are viruses specific for humans, some that only infect particular animals, some that infect plants, and even viruses that use bacteria as hosts. In current media reports of viral outbreaks in recent years, HIV, avian flu, swine flu, much is made of the origin of the virus with respect to its host/target organisms. However, most viruses are very specific about the cells that they infect. The narrow host range may be not only to particular species, but particular cell types within a particular species. Viruses with a broad host range are relatively rare. However, this does not preclude the possibility of new strains of virus evolving with different host ranges from their ancestral virii.
Viruses may have either RNA or DNA genomes, that may be linear or circular, and single or double -stranded. There are fewer variations of capsid structure. In general, capsids fall into two categories: helical and icosahedral. Helical capsids are actually made up of globular subunits that associate into a helical cylinder, with the genome lying inside an interior groove of the helix (fig. 1c). The icosahedral capsids are also made up of many subunits that together form an approximately 20-sided polygon made from sides that are equilateral (or nearly so) triangles. If you play Dungeons and DragonsTM or know someone who does, then you have probably seen dice (a “d20”) of this shape. Of course with capsids, but not dice, there can be some variation in the number of sides, the shape of the triangles, and the number of subunits that make up each face.
Figure 1. Viruses. (A) a T-4 bacteriophage, (B) adenovirus, (C) tobacco mosaic virus, (D) human immunodeciency virus, (E) influenza virus.
|Adenovirus||Adeno||Febrile respiratory disease; pharyngocojunctival fever|
|Hepatitis A||Picorna||Acute hepatitis|
|Hepatitis B||Hepadna||Acute/chronic hepatitis; Hepatic cirrhosis; hepatocellular carcinoma|
|Hepatitis C||Flavi||Similar to Hepatitis B|
|Herpes Simplex Type 1||Herpes||Cold sores, pharyngitis, gingivostomatitis|
|Herpes Simplex Type 2||Herpes||Aseptic meningitis; genital herpes|
External to the capsid, some viruses also have a membrane coat (viral envelope). As will be more clearly explained soon, this phospholipid bilayer comes from viruses that exit a host cell by exocytosis. Because it came from a host cell, the membrane can be used as a ruse by the virus to fool other potential host cells into misrecognizing the virus as a normal cell or cell debris, based on the receptors that recognize cellular proteins on the membrane. It may then be taken into the cell by receptor-mediated endocytosis in a mistaken attempt to recycle old cell debris, where it can proceed to infect the overgenerous host.
There are two classification systems for viruses, the International Committee on Taxonomy of Viruses (ICTV) has a Linnaean-like taxonomic system based on shared structural or biochemical properties (but not host specificity). Another system, also in use, is the Baltimore classification, in which viruses are classified into seven categories by the mechanism of mRNA production. That is, type I are the dsDNA viruses that make mRNA the “normal” way by direct transcription of the genome, type II are ssDNA viruses that must first make a complementary strand to become dsDNA before transcription, type VI are ssRNA viruses that use reverse transcriptase (detailed later in this section) to first convert the RNA to a DNA intermediate before transcription, and so on.