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M
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M
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TABLE OF CONTENTS
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INTRODUCTION
04
ORIGIN 05
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ANTIQUITY 07
MIDDLE AGES
09

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19TH CENTURY
10
20TH CENTURY
12
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CONTEMPORARY
18
BIBLIOGRAPHY
20
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INTRODUCTION

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Viruses are infectious agents with fairly
simple, acellular organization. They
possess only one type of nucleic acid,
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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
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 increase in the integrated sum of their
components & reproduce by division.
• Virus particles (virions) themselves do
not 'grow' or undergo division.

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• 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
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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.
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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
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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
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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
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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
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synthesized at specific times, into
infectious nucleic acids whose
replication could not be controlled. This
conjecture is supported by the
observation that the nucleic acids of
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retroviruses and a number of other
virions do contain sequences quite
similar to those of normal cells,
plasmids, and transposons.

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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
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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
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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
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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
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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,
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drawn in approximately 3700BC, which
depicts a temple priest called Ruma
showing typical clinical signs of
paralytic poliomyelitis.

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M
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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
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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.
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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.
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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
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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
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decline, may have been caused by
measles and smallpox viruses.

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M
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MIDDLE AGES

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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.
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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
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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
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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 M
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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,
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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
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19th CENTURY

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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. M
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M
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 LOUIS PASTEUR

The development in 1884 of the

porcelain bacterial filter by Charles
Chamberland, one of Pasteur’s
collaborators and inventor of the
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autoclave, made possible the discovery
of what are now called viruses. Tobacco
mosaic disease was the first to be
studied with Chamberland’s filter.

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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. M
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M
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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
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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
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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
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that the hoof-and-mouth disease of
cattle was also caused by a filterable
virus rather than by a toxin.

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M
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 IVANOWSKI

20TH CENTURY

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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. M
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M
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 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
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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
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Copenhagen reported that leukaemia
could be transmitted between chickens
by cell-free filtrates and was probably
caused by a virus.

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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
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established that at least some
malignancies were caused by viruses.
It was soon discovered that bacteria
themselves also could be attacked by

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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
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attack and destroy micrococci and
intestinal bacilli. Although he
speculated that his preparations might
contain viruses, Twort did not follow up
on these observations.
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M
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 FREDERICK W. TWORT FELIX
D’HERELLE

It remained for Felix d’Herelle to

establish decisively the existence of
bacterial viruses. D’Herelle isolated
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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
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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
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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

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(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
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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.
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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.

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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

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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
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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
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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
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elucidated in detail was tobacco
mosaic virus (TMV). In 1935, Wendell
Stanley achieved its crystallization for
electron microscopy and showed that it

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remains active even after
crystallization.
Clear X-ray diffraction pictures of the
crystallized virus were obtained by
Bernal and Fankuchen in 1941.
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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
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TMV RNA and its capsid (coat) protein
can assemble by themselves to form
functional viruses, suggesting that this
simple mechanism is likely the natural

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assembly mechanism within the host
cell.
In 1963, the Hepatitis B virus was
discovered by Baruch Blumberg who

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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
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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,

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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
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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
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human genome derives from such
retrotransposons.
In 1975 the functioning of oncoviruses
was clarified considerably. Until that
time, it was thought that these viruses
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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

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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.
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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
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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.
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A world-wide vaccination campaign led
by the UN World Health Organization
resulted in the eradication of smallpox
in 1979.

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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
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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
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cause of Kaposi's sarcoma which is
often seen in AIDS patients, was
identified in 1994. Several antiretroviral
drugs were developed in the late

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1990s, decreasing AIDS mortality
dramatically in developed countries.
The Hepatitis C virus was identified
using novel molecular cloning
techniques in 1987, leading to
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screening tests that dramatically
reduced the incidence of post-
transfusion hepatitis.
The first attempts at gene therapy
involving viral vectors began in the
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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
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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
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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.
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M
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M
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 CONTEMPORARY

21ST century started with the success of

gene therapy in X-linked SCID.
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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,
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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.
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The giant mimivirus, an intermediate
between tiny prokaryotes and ordinary
viruses, was described in 2003 and
sequenced in 2004.

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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
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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
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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 M
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BIBLIOGRAPHY

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http://jpkc.ynau.edu.cn/course/zwbl/shu
o/MolVirol/data/app3.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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M
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M
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