2009

MICROBIOLOGY ASSIGNMENT

SHIYAS
MSc BIOINFORMATICS
3/17/2009
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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
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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.
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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
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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
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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
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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.

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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
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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
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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
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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.
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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
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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
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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

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