Viruses infect all cellular life forms: eukaryotes (vertebrate animals, invertebrate animals, plants, fungi) and prokaryotes (bacteria and archaea). The viruses that infect bacteria are often referred to as bacteriophages, or phages for short.
The presence of viruses is obvious in host organisms showing signs of disease. Many healthy organisms, however, are hosts of non-pathogenic virus infections, some of which are active, while some are quiescent. Furthermore, the genomes of many organisms contain remnants of ancient virus genomes that integrated into their host genomes long ago. As well being present within their hosts, viruses are also found in soil, air and water. Many aqueous environments contain very high concentrations of viruses that infect the organisms that live in those environments.
There is a strong correlation between how intensively a species is studied and the number of viruses found in that species. Our own species is the subject of most attention as we have a vested interest in learning about agents that affect our health. It is not surprising that there are more viruses known that infect mankind than any other species, and new human viruses continue to be found. The intestinal bacterium Escherichia coli has also been the subject of much study and many viruses have been found in this species. If other species received the same amount of attention it is likely that many would be found to be hosts to similar numbers of viruses.
It is undoubtedly the case that the viruses that have been discovered represent only a tiny fraction of the viruses on the Earth. Most of the known plants, animals, fungi, bacteria and archaea have yet to be investigated for the presence of viruses, and new potential hosts for viruses continue to be discovered. Furthermore, the analysis of DNA from natural environments points to the existence of many bacterial species that have not yet been isolated in the laboratory; it is likely that these “non-cultivable bacteria” are also hosts to viruses.
1.2.1 Some viruses cause disease
Viruses are important agents of many human diseases, ranging from the trivial (e.g. common colds) to the lethal (e.g. rabies), and viruses also play roles in the development of several types of cancer. As well as causing individuals to suffer, virus diseases can also affect the well-being of societies. Smallpox had a great impact in the past and AIDS is having a great impact today.
There is therefore a requirement to understand the nature of viruses, how they replicate and how they cause disease. This knowledge permits the development of effective means for prevention, diagnosis, and treatment of virus diseases through the production of vaccines, diagnostic reagents and anti-viral drugs. Vaccines, such as rotavirus and measles vaccines, have saved millions of lives and improved the quality of life for millions more. Smallpox has been eradicated as a result of vaccination. Anti-viral drugs, such as those used against HIV and herpes simplex virus, play major roles in the treatment of infectious disease. Medical applications therefore constitute major aspects of the science of virology.
Many viruses cause disease in domestic animals (such as cattle, sheep, dogs, poultry, fish, and bees) and in wild animals (such as red squirrels and seals). Vaccines are used to control some of these diseases, for example foot and mouth disease and bluetongue. Crop plants are also hosts to large numbers of viruses, such as rice yellow mottle virus and cucumber mosaic virus, a virus with a very wide host range. These, and other plant viruses, can cause devastating outbreaks of disease in crop plants, with significant impact on the quantity and quality of food produced.
Another area where viruses can cause economic damage is in those industries where the products result from bacterial fermentation. In the dairy industry phages can destroy the lactic acid bacteria used to produce cheese, yogurt, and other milk products, while other phages can destroy Corynebacterium species used in the industrial production of amino acids.
1.2.2 Some viruses are useful
Some viruses are studied because they have useful current or potential applications.
- Phage typing of bacteria. Some groups of bacteria, such as some Salmonella species, are classified into strains on the basis of the spectrum of phages to which they are susceptible. Identification of the phage types of bacterial isolates can provide useful epidemiological information during outbreaks of disease caused by these bacteria.
- Sources of enzymes. A number of enzymes used in molecular biology are virus enzymes. Examples include reverse transcriptases from retroviruses and RNA polymerases from phages.
- Pesticides. Some insect pests are controlled with baculoviruses, and myxoma virus has been used to control rabbits.
- Anti-bacterial agents. In the mid-twentieth century phages were used to treat some bacterial infections in humans. Interest waned with the discovery of antibiotics, but has been renewed with the emergence of antibiotic-resistant strains of bacteria.
- Anti-cancer agents. Genetically modified strains of viruses, such as herpes simplex virus and vaccinia virus, are being investigated for treatment of cancers. These strains have been modified so that they are able to infect and destroy specific tumor cells, but are unable to infect normal cells.
- Gene vectors for protein production. Viruses, such as certain baculoviruses and adenoviruses, are used as vectors to take genes into animal cells growing in culture. This technology is used to make cells produce useful proteins, such as vaccine components. Some genetically modified cells are used for mass production of proteins.
- Gene vectors for treatment of genetic diseases. Children with the genetic disease Severe Combined Immunodeficiency (baby in the bubble syndrome) have been successfully treated using retroviruses as gene vectors. The viruses introduced into the children’s stem cells a non-mutated copy of the mutated gene (Section 17.5).
1.2.3 Virus studies have contributed to knowledge
Much basic knowledge of molecular biology, cell biology, and cancer has been derived from studies with viruses. Here are a few examples.
- A famous experiment carried by Alfred Hershey and Martha Chase, and published in 1952, used phage T2 and E. coli to provide strong evidence that genetic material is composed of DNA.
- The first enhancers to be characterized were in genes of simian virus 40 (SV40).
- The first transcription factor to be characterized was the transplantation (T) antigen of SV40.
- The first nuclear localization signal of a protein was identified in the T antigen of SV40.
- Introns were discovered during studies of adenovirus transcription.
- The role of the cap structure at the 5′ end of eukaryotic messenger RNA (mRNA) was discovered during studies with vaccinia virus and a reovirus.
- The first internal ribosome entry site to be discovered was found in the RNA of poliovirus.
- The first RNA pseudoknot to be discovered was in the genome of turnip yellow mosaic virus.
1.3.1 Viruses are small particles
Evidence for the existence of very small infectious agents was first provided in the late nineteenth century by two scientists working independently: Martinus Beijerinck in Holland and Dimitri Ivanovski in Russia. They made extracts from diseased plants, which we now know were infected with tobacco mosaic virus, and passed the extracts through fine filters. The filtrates contained an agent that was able to infect new plants, but no bacteria could be cultured from the filtrates. The agent remained infective through several transfers to new plants, eliminating the possibility of a toxin. Beijerinck called the agent a “virus” and the term has been in use ever since.
At around the same time, Friedrich Löeffler and Paul Frosch transmitted foot and mouth disease from animal to animal in inoculum that had been highly diluted. A few years later Walter Reed and James Carroll demonstrated that the causative agent of yellow fever is a filterable agent.
Figure 1.1 gives some indication of the size of these agents, which are known as virus particles or virions. The virion of a herpesvirus, which is a fairly large virus, is about ten million times smaller than a large balloon, while the balloon is smaller than the Earth by the same factor. The virions of most viruses are too small to be seen with a light microscope and can be seen only with an electron microscope (Figure 1.2).