The science of virusesvirology

• What is virology
• Virology history
• What is a virus
• Viruses and disease

Virology history A very early form of vaccination known In 1963, the Hepatitis B virus was as variolation was developed several discovered by Baruch Blumberg who went thousand years ago in China. It involved on to construct a vaccine against the application of materials from Hepatitis B. smallpox sufferers in order to immunize In 1965, Howard Temin described the others. In 1796 Edward Jenner used first retrovirus: a RNA-virus that was cowpox to successfully immunize a young able to insert its genome in the form of boy against smallpox, and this practice DNA into the host's genome. Reverse was widely adopted. Vaccinations against transcriptase, the key enzyme that other viral diseases followed, including retroviruses use to translate their RNA the successful rabies vaccination by into DNA, was first described in 1970, Louis Pasteur in 1886. The nature of independently by Howard Temin and David viruses however was not clear to these Baltimore. The first retrovirus researchers. infecting humans was identified by In 1892 Dimitri Ivanovski showed that a Robert Gallo in 1974. Later it was found disease of tobacco plants, tobacco that reverse transcriptase is not mosaic disease, could be transmitted by specific to retroviruses; extracts that were passed through retrotransposons which code for reverse filters fine enough to exclude even the transcriptase are abundant in the smallest known bacteria. In 1898 genomes of all eukaryotes. About 10-40% Martinus Beijerinck, also working on of the human genome derives from such tobacco plants, found that this retrotransposons. "filterable agent" grew in the host and In 1975 the functioning of oncoviruses was thus not a mere toxin. The question was clarified considerably. Until that of whether the agent was a "living time, it was thought that these viruses fluid" or a particle was however still carried certain genes called oncogenes open. which, when inserted into the host's In 1903 it was suggested for the first genome, would cause cancer. Michael time that transduction by viruses might Bishop and Harold Varmus showed that the cause cancer. Such an oncovirus in oncogene of Rous sarcoma virus is in chickens was described by Francis Peyton fact not specific to the virus but is Rous in 1911; it was later called Rous contained in healthy animals of many sarcoma virus 1 and understood to be a species. The oncovirus can switch this retrovirus. Several other cancer-causing pre-existing benign proto-oncogene on, retroviruses have since been described. turning it into a true oncogene. The existence of viruses that infect 1976 saw the first recorded outbreak of bacteria was first recognized by Ebola hemorrhagic fever, a highly lethal Frederick Twort in 1911, and, virally transmitted disease. independently, by Felix d'Herelle in In 1977, Frederick Sanger achieved the 1917. Since bacteria could be grown first complete sequencing of the genome easily in culture, this led to an of any organism, a bacteriophage. In the explosion of virology research. An same year, Richard Roberts and Phillip important investigator in this area, Max Sharp independently showed that the Delbrück, described the basic life genes of adenovirus contain introns and cycle of a virus in 1937: rather than therefore require gene splicing. It was "growing", a virus particle is assembled later realized that almost all genes of from its constituent pieces in one step; eukaryotes have introns as well. eventually it leaves the host cell to A world-wide vaccination campaign lead infect other cells. The Hershey-Chase by the UN World Health Organization lead experiment in 1952 showed that only DNA to the eradication of smallpox in 1979. and not protein enters a bacterial cell In 1982, Stanley Prusiner discovered upon infection with bacteriophage T2. prions and showed that they cause Transduction of bacteria by scrapie. bacteriophages was first described in The first cases of AIDS were reported in the same year. 1981, and HIV, the retrovirus causing While plant viruses and bacteriophages it, was identified in 1983 by Robert can be grown comparatively easily, Gallo and Luc Montagnier. Tests animal viruses normally require a living detecting HIV infection by detecting the host animal, which complicates their presence of HIV antibody were developed. study immensely. In 1931 it was shown Subsequent tremendous research efforts that influenza virus could be grown in turned HIV into the best studied virus. fertilized chicken eggs, a method that Human Herpes Virus 8, the cause of is still used today to produce vaccines. Kaposi's sarcoma which is often seen in In 1937, Max Theiler managed to grow the AIDS patients, was identified in 1994. yellow fever virus in chicken eggs and Several anti-retroviral drugs were produced a vaccine from an attenuated developed in the late 1990s, decreasing virus strain; this vaccine saved AIDS mortality dramatically in developed millions of lives and is still being countries. used today. The first attempts at gene therapy In 1949 John F. Enders, Thomas Weller involving viral vectors began in the and Frederick Robbins reported that they early 1980s, when retroviruses were had been able to grow poliovirus in developed that could insert a foreign cultured human embryonal cells, the gene into the host's genome. They first significant example of an animal contained the foreign gene but did not virus grown outside of animals and contain the viral genome and therefore chicken eggs. This work aided Jonas Salk could not reproduce. Tests in mice were in deriving a polio vaccine from killed followed by tests in humans, beginning polio viruses; this vaccine was shown to in 1989. The first human studies tried be effective in 1955. to correct the genetic disease severe The first virus which could be combined immunodeficiency (SCID), but crystalized and whose structure could clinical success was limited. In the therefore be elucidated in detail was period from 1990 to 1995, gene therapy tobacco mosaic virus (TMV), the virus was tried on several other diseases and that had been studied earlier by with different viral vectors, but it Ivanovski and Beijerink. In 1935, became clear that the initially high Wendell Stanley achieved its expectations were overstated. In 1999 a crystallization for electron microscopy further setback occurred when and showed that it remains active even 18-year-old Jesse Gelsinger died in a after crystallization. Clear X-ray gene therapy trial. He suffered a severe diffraction pictures of the crystallized immune response after having received an virus were obtained by Bernal and adenovirus vector. Success in the gene Fankuchen in 1941. Based on such therapy of two cases of X-linked SCID pictures, Rosalind Franklin proposed the was reported in 2000. full structure of the tobacco mosaic The giant mimivirus, in some sense an virus in 1955. Also in 1955, Heinz intermediate between tiny prokaryotes Fraenkel-Conrat and Robley Williams and ordinary viruses, was described in showed that purified TMV RNA and its 2003 and sequenced in 2004. capsid (coat) protein can assemble by Two vaccines protecting against several themselves to form functional virii, cervical cancer-causing strands of human suggesting that this simple mechanism is papillomavirus (HPV) were released in likely the natural assembly mechanism 2006. within the host cell. 1 A B 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80