History Of Virology

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SHIYAS MSc BIOINFORMATICS 1

3/17/2009

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INTRODUCTION

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ORIGIN

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ANTIQUITY

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MIDDLE AGES

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19TH CENTURY

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20TH CENTURY

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CONTEMPORARY

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BIBLIOGRAPHY

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TABLE OF CONTENTS

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INTRODUCTION

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Virus particles are produced from the assembly of pre-formed components, whereas other agents 'grow' from an increase in the integrated sum of their components & reproduce by division. Virus particles (virions) themselves do not 'grow' or undergo division. Viruses lack the genetic information which encodes apparatus necessary for the generation of metabolic energy or for protein synthesis (ribosomes).

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Viruses are infectious agents with fairly simple, acellular organization. They possess only one type of nucleic acid, either DNA or RNA, and only reproduce within living cells.

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The origin and subsequent evolution of viruses are shrouded in mystery, in part because of the lack of a fossil record. However, recent advances in the understanding of virus structure and reproduction have made possible more informed speculation on virus origins. At present there are two major hypotheses entertained by virologists. It has been proposed that at least some of the more complex enveloped viruses, such as the poxviruses and herpes viruses arose from small cells, probably prokaryotic, that parasitized larger, more complex cells. These parasitic cells would become ever simpler and more dependent on their hosts, much like multicellular parasites have done, in a process known as retrograde evolution. There are several problems with this hypothesis. Viruses are radically different from prokaryotes, and it is difficult to envision the mechanisms by which such a transformation might have occurred or the selective pressures leading to it. In addition, one would expect to find some forms intermediate between prokaryotes and at least the more complex enveloped viruses, but such forms have not been detected. The second hypothesis is that viruses represent cellular nucleic acids that have become partially independent of the cell. Possibly a few mutations could convert nucleic acids, which are only synthesized at specific times, into infectious nucleic acids

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ORIGIN

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whose replication could not be controlled. This conjecture is supported by the observation that the nucleic acids of retroviruses and a number of other virions do contain sequences quite similar to those of normal cells, plasmids, and transposons. The small, infectious RNAs called viroids have base sequences complementary to transposons, the regions around the boundary of mRNA introns, and portions of host DNA. This has led to speculation that they have arisen from introns or transposons. It is possible that viruses have arisen by way of both mechanisms. Because viruses differ so greatly from one another, it seems likely that they have originated independently many times during the course of evolution. Probably many viruses have evolved from other viruses just as cellular organisms have arisen from specific predecessors.

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ANTIQUITY

The Pharaoh Siptah ruled Egypt from 1200-1193 BC when he died suddenly at the age of about 20. His mummified body lay undisturbed in his tomb in the Valley of the Kings until 1905 when the tomb was excavated. The mummy shows that his left leg was withered and his foot was rigidly extended like a horse's hoof - classic paralytic poliomyelitis. Pharaoh Ramses V, who died in 1196BC, is believed to have succumbed to smallpox - compare the pustular lesions on the face of the mummy & those of more recent patients. Smallpox was endemic in China by 1000BC. In response, the practice of variolation was developed. Recognizing that survivors of smallpox outbreaks were protected from subsequent infection, variolation involved inhalation of the dried

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Ancient peoples were not only aware of the effects of virus infection, but in some instances also carried out research into the causes & prevention of virus diseases. The first written record of a virus infection consists of a hieroglyph from Memphis, the capital of ancient Egypt, drawn in approximately 3700BC, which depicts a temple priest called Ruma showing typical clinical signs of paralytic poliomyelitis.

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crusts from smallpox lesions like snuff, or in later modifications, inoculation of the pus from a lesion into a scratch on the forearm of a child.

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There is some evidence that the great epidemics of A.D. 165 to 180 and A.D. 251 to 266, which severely weakened the Roman Empire and aided its decline, may have been caused by measles and smallpox viruses.

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MIDDLE AGES

Later in the century an English country doctor, Edward Jenner, stimulated by a girl’s claim that she could not catch smallpox because she had had cowpox, began inoculating humans with material from cowpox lesions. He published the results of 23 successful vaccinations in 1798. Although Jenner did not understand the nature of smallpox, he did manage to successfully protect his patients from the dread disease through exposure to the cowpox virus.

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Smallpox had an equally profound impact on the New World. Hernán Cortés’s conquest of the Aztec Empire in Mexico was made possible by an epidemic that ravaged Mexico City. The virus was probably brought to Mexico in 1520 by the relief expedition sent to join Cortés. Before the smallpox epidemic subsided, it had killed the Aztec King Cuitlahuac (the nephew and son-in-law of the slain emperor, Montezuma II) and possibly 1/3 of the population. The first progress in preventing viral diseases came years before the discovery of viruses. Early in the eighteenth century, Lady Wortley Montagu, wife of the English ambassador to Turkey, observed that Turkish women inoculated their children against smallpox. The children came down with a mild case and subsequent were immune. Lady Montagu tried to educate the English public about the procedure but without great success.

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19th CENTURY Into the nineteenth century, harmful agents were often grouped together and sometimes called viruses [Latin virus, poison or venom]. Even Louis Pasteur used the term virus for any living infectious disease agent.

The development in 1884 of the porcelain bacterial filter by Charles Chamberland, one of Pasteur’s collaborators and inventor of the autoclave, made possible the discovery of what are now called viruses. Tobacco mosaic disease was the first to be studied with Chamberland’s filter. In 1892 Dmitri Ivanowski published studies showing that leaf extracts from infected plants would induce tobacco mosaic disease even after filtration to remove bacteria. He attributed this to the presence of a toxin.

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LOUIS PASTEUR

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TOBACCO MOSAIC VIRUS AFFECTED LEAF

IVANOWSKI

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Martinus W. Beijerinck, working independently of Ivanowski, published the results of extensive studies on tobacco mosaic disease in 1898 and 1900. Because the filtered sap of diseased plants was still infectious, he proposed that the disease was caused by an entity different from bacteria, a filterable virus. He observed that the virus would multiply only in living plant cells, but could survive for long periods in a dried state. At the same time Friedrich Loeffler and Paul Frosch in Germany found that the hoof-and-mouth disease of cattle was also caused by a filterable virus rather than by a toxin.

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20TH CENTURY In 1900 Walter Reed began his study of the yellow fever disease whose incidence had been increasing in Cuba. Reed showed that this human disease was due to a filterable virus that was transmitted by mosquitoes.

Mosquito control shortly reduced the severity of the yellow fever problem. Thus by the beginning of this century, it had been established that filterable viruses were different from bacteria and, Could cause diseases in plants, livestock, and humans. Shortly after the turn of the century, Vilhelm Ellermann and Oluf Bang in Copenhagen reported that leukaemia could be transmitted between chickens by cell-free filtrates and was probably caused by a virus. Three years later in 1911, Peyton Rous from the Rockefeller Institute in New York City reported that a virus was responsible for a malignant muscle tumour in chickens. These studies established that at least some malignancies were caused by viruses.

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WALTER REED

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It was soon discovered that bacteria themselves also could be attacked by viruses. The first published observation suggesting that This might be the case was made in 1915 by Frederick W. Twort. Twort isolated bacterial viruses that could attack and destroy micrococci and intestinal bacilli. Although he speculated that his preparations might contain viruses, Twort did not follow up on these observations.

FELIX D’HERELLE

It remained for Felix d’Herelle to establish decisively the existence of bacterial viruses. D’Herelle isolated bacterial viruses from patients with dysentery, probably caused by Shigella dysenteriae. He noted that when a virus suspension was spread on a layer of bacteria growing on agar, clear circular areas containing viruses and lysed cells developed. A count of these clear zones allowed d’Herelle to estimate the number of viruses present. D’Herelle demonstrated that these viruses could reproduce only in live bacteria; therefore he named them bacteriophages because they could eat holes in bacterial “lawns.”

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FREDERICK W. TWORT

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The chemical nature of viruses was established when Wendell M. Stanley announced in 1935 that he had crystallized the tobacco mosaic virus (TMV) and found it to be largely or completely protein. A short time later Frederick C. Bawden and Norman W. Pirie managed to separate the TMV virus particles into protein and nucleic acid. Thus by the late 1930s it was becoming clear that viruses were complexes of nucleic acids and proteins able to reproduce only in living cells. In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, Max Theiler managed to grow the yellow fever virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today. In 1949 John F. Enders, Thomas Weller and Frederick Robbins reported that they had been able to grow poliovirus in cultured human embryonic cells, the first significant example of an animal virus grown outside of animals or chicken eggs. This work aided Jonas Salk in deriving a polio vaccine from killed polio viruses; this vaccine was shown to be effective in 1955. The first virus that could be crystallized and whose structure could therefore be elucidated in detail was tobacco mosaic virus (TMV). In 1935, Wendell Stanley achieved its crystallization for electron microscopy and showed that it remains active even after crystallization.

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Clear X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, Rosalind Franklin proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA and its capsid (coat) protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism is likely the natural assembly mechanism within the host cell. In 1963, the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a vaccine against Hepatitis B. In 1965, Howard Temin described the first retrovirus: an RNAvirus that was able to insert its genome in the form of DNA into the host's genome. 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. The first retrovirus infecting humans was identified by Robert Gallo in 1974. Later it was found that reverse transcriptase is not specific to retroviruses; retrotransposons which code for reverse transcriptase are abundant in the genomes of all eukaryotes. About 10-40% of the human genome derives from such retrotransposons. In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogenes which, when inserted into the host's genome, would cause cancer. Michael Bishop and Harold Varmus showed that the oncogene of Rous

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contained in healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene that causes cancer. 1976 saw the first recorded outbreak of Ebola hemorrhagic fever, a highly lethal virally transmitted disease. In 1977, Frederick Sanger achieved the first complete sequencing of the genome of any organism, the bacteriophages Phi X 174. In the same year, Richard Roberts and Phillip Sharp independently showed that the genes of adenovirus contain introns and therefore require gene splicing. It was later realized that almost all genes of eukaryotes have introns as well. A world-wide vaccination campaign led by the UN World Health Organization resulted in the eradication of smallpox in 1979. In 1982, Stanley Prusiner discovered prions and showed that they cause scrapie. The first cases of AIDS were reported in 1981, and HIV, the retrovirus causing it, was identified in 1983 by Robert Gallo and Luc Montagnier. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Human Herpes Virus 8, the cause of Kaposi's sarcoma which is often seen in AIDS patients, was identified in 1994. Several antiretroviral drugs were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries. The Hepatitis C virus was identified using novel molecular cloning techniques in 1987, leading to screening tests that dramatically reduced the incidence of post-transfusion hepatitis.

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sarcoma virus is in fact not specific to the virus but is

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The first attempts at gene therapy involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in humans, beginning in 1989. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-yearold Jesse Gelsinger died in a gene therapy trial. He suffered a severe immune response after having received an adenovirus vector.

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21ST century started with the success of gene therapy in X-linked SCID. In 2002 it was reported that poliovirus had been synthetically assembled in the laboratory, representing the first synthetic organism. Assembling the 7741-base genome from scratch, starting with the virus's published RNA sequence, took about two years. In 2003 a faster method was shown to assemble the 5386-base genome of the bacteriophages Phi X 174 in 2 weeks. The giant mimivirus, an intermediate between tiny prokaryotes and ordinary viruses, was described in 2003 and sequenced in 2004. The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu pandemic in 1918 was reconstructed in 2005. Sequence information was pieced together from preserved tissue samples of flu victims; viable virus was then synthesized from this sequence.[4] By 1985, Harald zur Hausen had shown that two strains of Human papillomavirus (HPV) cause most cases of cervical cancer. Two vaccines protecting against these strains were released in 2006.

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CONTEMPORARY

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In 2006 and 2007 it was reported that introducing a small number of specific transcription factor genes into normal skin cells of mice or humans can turn these cells into pluripotent stem cells, known as Induced Pluripotent Stem Cells. The technique uses modified retroviruses to transform the cells; this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host's genome, which can interrupt other genes and potentially causes cancer.

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BIBLIOGRAPHY

http://jpkc.ynau.edu.cn/course/zwbl/shuo/MolVirol/data/app 3.htm

www.wikipaedia .com

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Prescott, Harley and Klein's ; 5th edition; October 2002; The McGraw−Hill Companies ; Pg No: 362-364

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