structure

Most viruses that have been studied have a diameter between 10 and 300 nanometres. Some filoviruses have a total length of up to 1400 nm, however their diameters are only about 80 nm.^[3]

A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid.

These are formed from identical protein subunits called capsomers.^[53]

Viruses can have a lipid "envelope" derived from the host cell membrane.

The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction.^[54][55]

Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid.

In general, there are four main morphological virus types:

Helical capsids are composed of a single type of capsomer stacked around a central axis to form a helical structure, which may have a central cavity, or hollow tube. This arrangement results in rod-shaped or filamentous virions: these can be short and highly rigid, or long and very flexible. The genetic material, generally single-stranded RNA, but ssDNA in some cases, is bound into the protein helix, by interactions between the negatively-charged nucleic acid and positive charges on the protein. Overall, the length of a helical capsid is related to the length of the nucleic acid contained within it and the diameter is dependent on the size and arrangement of capsomers. The well-studied Tobacco mosaic virus is an example of a helical virus.^[56]

Most animal viruses are icosahedral or near-spherical with icosahedral symmetry. A regular icosahedron is the optimum way of forming a closed shell from identical sub-units. The minimum number of identical capsomers required is twelve, each composed of five identical sub-units. Many viruses, such as rotavirus, have more than twelve capsomers and appear spherical but they retain this symmetry. Capsomers at the apices are surrounded by five other capsomers and are called pentons. Capsomers on the triangular faces are surround by six others and are call hexons.^[57]

Some species of virus envelope themselves in a modified form of one of the cell membranes, either the outer membrane surrounding an infected host cell, or internal membranes such as nuclear membrane or endoplasmic reticulum, thus gaining an outer lipid bilayer known as a viral envelope. This membrane is studded with proteins coded for by the viral genome and host genome; the lipid membrane itself and any carbohydrates present originate entirely from the host. The influenza virus and HIV use this strategy. Most enveloped viruses are dependent on the envelope for their infectivity.^[58]

Complex

The structure of a typical bacteriophage

These viruses possess a capsid that is neither purely helical, nor purely icosahedral, and that may possess extra structures such as protein tails or a complex outer wall. Some bacteriophages have a complex structure consisting of an icosahedral head bound to a helical tail, which may have a hexagonal base plate with protruding protein tail fibres.

The poxviruses are large, complex viruses that have an unusual morphology. The viral genome is associated with proteins within a central disk structure known as a nucleoid. The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole particle is slightly pleiomorphic, ranging from ovoid to brick shape.^[59] Mimivirus is the largest known virus, with a capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral.^[60]

origins

The origin of viruses is unclear because they do not form fossils, so molecular techniques have been the most useful means of investigating how they arose. These techniques rely on the availability of ancient viral DNA or RNA, but, unfortunately, most of the viruses that have been preserved and stored in laboratories are less than 90 years old.

There are three main theories of the origins of viruses:^[30][31]

• Regressive theory: Viruses may have once been small cells that parasitised larger cells. Over time, genes not required by their parasitism were lost. The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend credence to this theory, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. This is also called the degeneracy theory.^[32][33]

• Cellular origin theory (sometimes called the vagrancy theory):^[32][34] Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. The escaped DNA could have come from plasmids (pieces of naked DNA that can move between cells) ortransposons (molecules of DNA that replicate and move around to different positions within the genes of the cell).^[35] Once called "jumping genes", transposons are examples of mobile genetic elements and could be the origin of some viruses. They were discovered in maize by Barbara McClintock in 1950.^[36]

• Coevolution theory: Viruses may have evolved from complex molecules of protein and nucleic acid at the same time as cells first appeared on earth and would have been dependent on cellular life for many millions of years. Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. However, they have characteristics that are common to several viruses and are often called subviral agents.^[37] Viroids are important pathogens of plants.^[38] They do not code for proteins but interact with the host cell and use the host machinery for their replication.^[39]The hepatitis delta virus of humans has an RNA genome similar to viroids but has protein coat derived from hepatitis B virus and cannot produce one of its own. It is therefore a defective virus and cannot replicate without the help of hepatitis B virus.^[40]

The Virophage 'sputnik' infects the Mimivirus and the related Mamavirus, which in turn infect the protozooan Acanthamoeba castellanii.^[41] These viruses that are dependent on other virus species are called satellites and may represent evolutionary intermediates of viroids and viruses.^[42][43]

Prionsare infectious protein molecules that do not contain DNA or RNA.^[44] They cause an infection in sheep called scrapie and cattle bovine spongiform encephalopathy ("mad cow" disease). In humans they cause kuru and Creutzfeld-Jacob disease.^[45] They are able to replicate because some proteins can exist in two different shapes and the prion changes the normal shape of a host protein into the prion shape. This starts a chain reaction where each prion protein converts many host proteins into more prions, and these new prions then go on to convert even more protein into prions. Although they are fundamentally different from viruses and viroids, their discovery gives credence to theory that viruses could have evolved from self-replicating molecules.^[46]

It seems unlikely that all currently known viruses have a common ancestor and viruses have probably arisen numerous times in the past by one or more mechanisms.^[47]

Opinions differ on whether viruses are a form of life, or organic structures that interact with living organisms. They have been described as "organisms at the edge of life",^[48] since they resemble organisms in that they possess genes and evolve by natural selection,^[49] and reproduce by creating multiple copies of themselves through self-assembly. However, although they have genes, they do not have a cellular structure, which is often seen as the basic unit of life. Additionally, viruses do not have their own metabolism, and require a host cell to make new products. They therefore cannot reproduce outside a host cell (though bacterial species such as rickettsia and chlamydia are considered living organisms despite the same limitation). Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells, which is analogous to the autonomous growth of crystals. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules.^[50]

history

In 1884, Charles Chamberland created a filter with pores smaller than bacteria.

He could pass a solution through it and completely remove bacteria from the solution.

In 1892, Dimitri Ivanoski used the filter to study what is now known as tobacco mosaic virus.

He showed that crushed leaf extracts from infected tobacco plants were still infectious after passing through the filter (remember, viruses are 100 times smaller than bacteria). He suggested that the infection might be caused by a toxin produced by bacteria but did not pursue the idea.

At that time it was thought that all infectious agents

* could be retained by filters (too large for viruses)

* grown on a nutrient medium (viruses need host cells to grow)

In 1898 Martinus Beijerinck repeated the experiments and became convinced this was a new type of infectious agent. He observed that the agent multiplied only in dividing cell and used the word virus but thought it was liquid in nature.

In 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.

In the early 20th century, the English bacteriologist Frederick Twort discovered the viruses that infect bacteria, which are now called bacteriophages.

the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria 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.

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.^[12] 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.

Another breakthrough came in 1931, when the American pathologist Ernest William Goodpasture grew influenza and several other viruses in fertilised chickens' eggs.^[14] 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.^[15]

With the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll came the first images of viruses.^[16] In 1935 American biochemist and virologist Wendell Stanley examined the Tobacco mosaic virus and found it to be mostly made from protein.^[17]

A short time later, this virus was separated into protein and RNA parts.

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.^[19] 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.^[20]