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2009

SHIYAS

MSc BIOINFORMATICS

3/17/2009

MICROBIOLOGY ASSIGNMENT

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TABLE OF CONTENTS

INTRODUCTION 04

ORIGIN 05

ANTIQUITY 07

MIDDLE AGES 09

19TH CENTURY 10

20TH CENTURY 12

CONTEMPORARY 18

BIBLIOGRAPHY 20

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INTRODUCTION

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.

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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ORIGIN

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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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

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.

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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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.

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

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.

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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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.

LOUIS PASTEUR

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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TOBACCO MOSAIC VIRUS AFFECTED LEAF

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.

IVANOWSKI

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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.

WALTER REED

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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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.

FREDERICK W. TWORT 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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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 RNA-virus 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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sarcoma virus is in fact not specific to the virus but is 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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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-year-old Jesse Gelsinger died in a gene therapy trial. He suffered a

severe immune response after having received an adenovirus vector.

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CONTEMPORARY

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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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

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