Virus (life science)

V

Defense

Although viruses cannot be treated with antibiotics, which are effective only against bacteria, the body’s immune system has many natural defenses against virus infections. Infected cells produce interferons and other cytokines (soluble components that are largely responsible for regulating the immune response), which can signal adjacent uninfected cells to mount their defenses, enabling uninfected cells to impair virus replication. Some cytokines can cause a fever in response to viral infection; elevated body temperature retards the growth of some types of viruses. B lymphocytes produce specific antibodies that can bind and inactivate viruses. Cytotoxic T cells recognize virus-infected cells and target them for destruction. However, many viruses have evolved ways to circumvent some of these host defense mechanisms.

The development of antiviral therapies has been thwarted by the difficulty of generating drugs that can distinguish viral processes from cellular processes. Therefore, most treatments for viral diseases simply alleviate symptoms, such as fever, dehydration, and achiness. Nevertheless, antiviral drugs for influenza virus, herpesviruses, and HIV are available, and many others are in the experimental and developmental stages.

Prevention has been a more effective method of controlling virus infections. Viruses that are transmitted by insects or rodent excretions can be controlled with pesticides. Successful vaccines are currently available for poliovirus, influenza, rabies, adenovirus, rubella, yellow fever, measles, mumps, and chicken pox. Vaccines are prepared from killed (inactivated) virus, live (attenuated or weakened) virus, or isolated viral proteins (subunits). Each of these types of vaccines elicits an immune response while causing little or no disease, and there are advantages and disadvantages to each. (For a more complete discussion of vaccines, see the Immunization article.)

The principle of vaccination was discovered by British physician Edward Jenner. In 1796 Jenner observed that milkmaids in England who contracted the mild cowpox virus infection from their cows were protected from smallpox, a frequently fatal disease. In 1798 Jenner formally demonstrated that prior infection with cowpox virus protected those that he inoculated with smallpox virus (an experiment that would not meet today’s protocol standards because of its use of human subjects). In 1966 the World Health Organization (WHO) initiated a program to eradicate smallpox from the world. Because it was impossible to vaccinate the entire world population, the eradication plan was to identify cases of smallpox and then vaccinate all of the individuals in that vicinity. The last reported case of smallpox was in Somalia in October 1977. An important factor in the success of eradicating smallpox was that humans are the only host and there are no animal reservoirs for smallpox virus. The strain of poxvirus used for immunization against smallpox was called vaccinia. Introduction of the Salk (inactivated) and Sabin (live, attenuated) vaccines for poliovirus, developed in the 1950s by the American physician and epidemiologist Jonas Salk and the American virologist Albert Bruce Sabin, respectively, was responsible for a significant worldwide decline in paralytic poliomyelitis. However, polio has not been eradicated, partly because the virus can mutate and escape the host immune response. Influenza viruses mutate so rapidly that new vaccines are developed for distribution each year.

---

---

Viruses undergo very high rates of mutation (genetic alteration) largely because they lack the repair systems that cells have to safeguard against mutations. A high mutation rate enables the virus to continually adapt to new intracellular environments and to escape from the host immune response. Co-infection of the same cell with different related viruses allows for genetic reassortment (exchange of genome segments) and intramolecular recombination. Genetic alterations can alter virulence or allow viruses to gain access to new cell types or new animal hosts. Many scientists believe that HIV is derived from a closely related monkey virus, SIV (simian immunodeficiency virus), that acquired the ability to infect humans. Many of today’s emerging viruses may have similar histories.

VI

Discovery

By the last half of the 19th century, the microbial world was known to consist of protozoa, fungi, and bacteria, all visible with a light microscope. In the 1840s, the German scientist Jacob Henle suggested that there were infectious agents too small to be seen with a light microscope, but for the lack of direct proof, his hypothesis was not accepted. Although the French scientist Louis Pasteur was working to develop a vaccine for rabies in the 1880s, he did not understand the concept of a virus.

During the last half of the 19th century, several key discoveries were made that set the stage for the discovery of viruses. Pasteur is usually credited for dispelling the notion of spontaneous generation and proving that organisms reproduce new organisms. The German scientist Robert Koch, a student of Jacob Henle, and the British surgeon Joseph Lister developed techniques for growing cultures of single organisms that allowed the assignment of specific bacteria to specific diseases.

The first experimental transmission of a viral infection was accomplished in about 1880 by the German scientist Adolf Mayer, when he demonstrated that extracts from infected tobacco leaves could transfer tobacco mosaic disease to a new plant, causing spots on the leaves. Because Mayer was unable to isolate a bacterium or fungus from the tobacco leaf extracts, he considered the idea that tobacco mosaic disease might be caused by a soluble agent, but he concluded incorrectly that a new type of bacteria was likely to be the cause. The Russian scientist Dimitri Ivanofsky extended Mayer’s observation and reported in 1892 that the tobacco mosaic agent was small enough to pass through a porcelain filter known to block the passage of bacteria. He too failed to isolate bacteria or fungi from the filtered material. But Ivanofsky, like Mayer, was bound by the dogma of his times and concluded in 1903 that the filter might be defective or that the disease agent was a toxin rather than a reproducing organism.

Unaware of Ivanofsky’s results, the Dutch scientist Martinus Beijerinck, who collaborated with Mayer, repeated the filter experiment but extended this finding by demonstrating that the filtered material was not a toxin because it could grow and reproduce in the cells of the plant tissues. In his 1898 publication, Beijerinck referred to this new disease agent as a contagious living liquid—contagium vivum fluid—initiating a 20-year controversy over whether viruses were liquids or particles.

The conclusion that viruses are particles came from several important observations. In 1917 the French-Canadian scientist Félix H. d’Hérelle discovered that viruses of bacteria, which he named bacteriophage, could make holes in a culture of bacteria. Because each hole, or plaque, developed from a single bacteriophage, this experiment provided the first method for counting infectious viruses (the plaque assay). In 1935 the American biochemist Wendell Meredith Stanley crystallized tobacco mosaic virus to demonstrate that viruses had regular shapes, and in 1939 tobacco mosaic virus was first visualized using the electron microscope.

In 1898 the German bacteriologists Friedrich August Johannes Löffler and Paul F. Frosch (both trained by Robert Koch) described foot-and-mouth disease virus as the first filterable agent of animals, and in 1900, the American bacteriologist Walter Reed and colleagues recognized yellow fever virus as the first human filterable agent. For several decades viruses were referred to as filterable agents, and gradually the term virus (Latin for “slimy liquid” or “poison”) was employed strictly for this new class of infectious agents. Through the 1940s and 1950s many critical discoveries were made about viruses through the study of bacteriophages because of the ease with which the bacteria they infect could be grown in the laboratory. Between 1948 and 1955, scientists at the National Institutes of Health (NIH) and at Johns Hopkins Medical Institutions revolutionized the study of animal viruses by developing cell culture systems that permitted the growth and study of many animal viruses in laboratory dishes.

VII

Evolution

Three theories have been put forth to explain the origin of viruses. One theory suggests that viruses are derived from more complex intracellular parasites that have eliminated all but the essential features required for replication and transmission. A more widely accepted theory is that viruses are derived from normal cellular components that gained the ability to replicate autonomously. A third possibility is that viruses originated from self-replicating RNA molecules. This hypothesis is supported by the observation that RNA can code for proteins as well as carry out enzymatic functions. Thus, viroids may resemble “prehistoric” viruses.

VIII

Importance of Viruses

Because viral processes so closely resemble normal cellular processes, abundant information about cell biology and genetics has come from studying viruses. Basic scientists and medical researchers at university and hospital laboratories are working to understand viral mechanisms of action and are searching for new and better ways to treat viral illnesses. Many pharmaceutical and biotechnology companies are actively pursuing effective antiviral therapies. Viruses can also serve as tools. Because they are efficient factories for the production of viral proteins, viruses have been harnessed to produce a wide variety of proteins for industrial and research purposes. A new area of endeavor is the use of viruses for gene therapy. Because viruses are programmed to carry genetic information into cells, they have been used to replace defective cellular genes. Viruses are also being altered by genetic engineering to kill selected cell populations, such as tumor cells. The use of genetically engineered viruses for medical intervention is a relatively new field, and none of these therapies is widely available. However, this is a fast-growing area of research, and many clinical trials are now in progress. The use of genetically engineered viruses extends beyond the medical field. Recombinant insect viruses have agricultural applications and are currently being tested in field trials for their effectiveness as pesticides.

	More from Encarta
	•  7 tips for funding an online degree •  How to succeed in the fashion industry without being a top designer •  Presidential Myths Quiz •  Coffee break: Recharge your brain