A virus (from the Latin virus meaning toxin or poison) is a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell. Viruses infect all cellular life. The first known virus, tobacco mosaic virus, was discovered by Martinus Beijerinck in 1899,[1] and now more than 5,000 types of virus have been described.[2] The study of viruses is known as virology, and is a branch of microbiology.
Viruses consist of two or three parts: all viruses have genes made from either DNA or RNA, long molecules that carry genetic information; all have a protein coat that protects these genes; and some have an envelope of fat that surrounds them when they are outside a cell. Viruses vary in shape from simple helical and icosahedral shapes, to more complex structures. They are about 100 times smaller than bacteria.[3] The origins of viruses are unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.
Viruses spread in many ways; different species of virus use different methods. For example, plant viruses are often transmitted from plant to plant by insects that feed on sap, such as aphids, while animal viruses can be carried by blood-sucking insects. These disease-bearing organisms are known as vectors. Influenza viruses are spread by coughing and sneezing, and others such as norovirus, are transmitted by the faecal-oral route, when they contaminate hands, food or water. Rotavirus is often spread by direct contact with infected children. HIV is one of several viruses that are transmitted through sex.
Not all viruses cause disease, as many viruses reproduce without causing any obvious harm to the infected organism. Some viruses such as HIV can cause life-long or chronic infections, and the viruses continue to replicate in the body despite the hosts' defence mechanisms. However, viral infections in animals usually cause an immune response, which can completely eliminate a virus. These immune responses can also be produced by vaccines that give lifelong immunity to a viral infection. Microorganisms such as bacteria also have defences against viral infection, such as restriction modification systems. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections.In 1884, the French microbiologist Charles Chamberland invented a filter, (known today as the Chamberland filter or Chamberland-Pasteur filter), with pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them from the solution.[7] In 1892 the Russian biologist Dimitri Ivanovski used this filter to study what is now known to be tobacco mosaic virus. His experiments showed that the crushed leaf extracts from infected tobacco plants are still infectious after filtration. Ivanovski suggested the infection might be caused by a toxin produced by bacteria, but did not pursue the idea.[8] At the time it was thought that all infectious agents could be retained by filters and grown on a nutrient medium—this was part of the germ theory of disease.[9] In 1899 the Dutch microbiologist Martinus Beijerinck repeated the experiments and became convinced that this was a new form of infectious agent.[10] He went on to observe that the agent multiplied only in dividing cells, but as his experiments did not show that it was made of particles, he called it a contagium vivum fluidum (soluble living germ) and re-introduced the word virus.[8] Beijerinck maintained that viruses were liquid in nature, a theory later discredited by Wendell Stanley, who proved they were particulate.[8] In the same year, 1899, Friedrich Loeffler and Frosch passed the agent of foot and mouth disease (aphthovirus) through a similar filter and ruled out the possibility of a toxin because of the high dilution; they concluded that the agent could replicate.[8]
In the early 20th century, the English bacteriologist Frederick Twort discovered the viruses that infect bacteria, which are now called bacteriophages,[11] and the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria growing on agar, would produce areas of dead bacteria. He accurately diluted a suspension of these viruses and discovered that the highest dilutions, rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the suspension.[12]
By the end of the nineteenth century, viruses were defined in terms of their infectivity, filterability, and their requirement for living hosts. Viruses had only been grown in plants and animals. In 1906, Harrison invented a method for growing tissue in lymph, and, in 1913, E. Steinhardt, C. Israeli and R. A. Lambert used this method to grow vaccinia virus in fragments of guinea pig corneal tissue.[13] In 1928, H. B. Maitland and M. C. Maitland grew vaccinia virus in suspensions of minced hens' kidneys. Their method was not widely adopted until the 1950s, when poliovirus was grown on a large scale for vaccine production.[14]
Another breakthrough came in 1931, when the American pathologist Ernest William Goodpasture grew influenza and several other viruses in fertilised chickens' eggs.[15] In 1949 John F. Enders, Thomas Weller and Frederick Robbins grew polio virus in cultured human embryo cells, the first virus to be grown without using solid animal tissue or eggs. This work enabled Jonas Salk to make an effective polio vaccine.[16]
Rosalind Franklin
With the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll came the first images of viruses.[17] In 1935 American biochemist and virologist Wendell Stanley examined the Tobacco mosaic virus and found it to be mostly made from protein.[18] A short time later, this virus was separated into protein and RNA parts.[19] Tobacco mosaic virus was the first one to be crystallised and whose structure could therefore be elucidated in detail. The first X-ray diffraction pictures of the crystallised virus were obtained by Bernal and Fankuchen in 1941. Based on her pictures, Rosalind Franklin discovered the full structure of the virus in 1955.[20] In the same year, Heinz Fraenkel-Conrat and Robley Williams showed that purified Tobacco mosaic virus RNA and its coat protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism was probably how viruses assembled within their host cells.[21]
The second half of the twentieth century was the golden age of virus discovery and most of the 2,000 recognised species of animal, plant and bacterial viruses were discovered during these years.[1][22] In 1957, equine arterivirus and the cause of Bovine virus diarrhea (a pestivirus) were discovered. In 1963, the hepatitis B virus was discovered by Baruch Blumberg,[23] and in 1965, Howard Temin described the first retrovirus. Reverse transcriptase, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and David Baltimore.[24] In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV.
