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UNDERSTANDING
THE
VIRUSES
JOSELITO DG. DAR
Department of Biological Sciences
College of Arts and Sciences
Central Luzon State University
Science City of Muñoz
November 2003
Chapter 1
Introduction
Virology is a branch of microbiology that
deals with the study of viruses. Viruses are
acellular, ultramicroscopic, obligatory parasitic
entities having DNA or RNA as genetic material.
The genetic material of viruses is enclosed in a
protein shell called capsid. The capsid may be
surrounded by a lipid-containing membrane.
Viruses have been one of the main causes of
epidemics worldwide and throughout the history of
man.
This chapter discusses the history and origin
of viruses, as well as enumerates some scientists,
their contribution in the development of this field of
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science and lists some of the common terminologies
being used in the field.
A. Origin of Viruses
Up to the present, the origin of viruses is
still unclear and is always a subject for debate and
discussion. Scientists have proposed three theories,
these are:
Regressive evolution - viruses are degenerate
life-forms which have lost many functions
that other organisms still possess. Viruses
have only retained the genetic information
essential to their parasitic way of life.
Cellular origins - viruses are acellular,
Functional assemblies of macromolecules
which have escaped their origins inside their
hosts’ cells.
Independent entities - viruses
evolved on
A parallel course along with other cellular
organisms
from
the
self-replicating
molecules believed to have existed in the
primitive pre-biotic 'RNA world'.
These theories have their own supporters
and the subject provokes debates. What matters is
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that viruses really do exist, and we are all
susceptible to be infected by them.
The importance of the origin of viruses is
that it may have practical implications for
virologists. Such ideas may allow us to predict the
properties and behaviors of new viruses, or to
develop new drugs based on what is already known
about existing viruses.
B. Historical Background
Ancient people might have been plagued
with viral diseases, but most of these were thought
to have been brought by a Super-natural being due
to their sins.
A hieroglyph (Fig. 1a) drawn around 3,700
BCE was found in Memphis, the capital of ancient
Egypt.
The hieroglyph depicted the temple priest
named Ruma. It could be noticed that the right leg
of the priest shows a typical clinical signs of
parasitic poliomyelitis, which is caused by a virus.
Perhaps, this could be the earliest written record of
viral infection.
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Fig. 1.a Hieroglyph from Memphis
The pharaoh Siptah, who ruled Egypt in
1200 – 1193 BCE, died at an early age of 20. His
body was mummified like all pharaohs. When his
tomb was opened and his mummy unearthed,
scientists have discovered that his left foot (Fig. 1.b)
was rigidly extended like a horse's hoof, another
classic paralytic poliomyelitis case.
Fig. 1.b Right foot of Siptah
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Another proof of viral infection was noted
when the mummy of the great pharaoh Ramses V,
who died in 1196 BCE, was discovered.
The face of the mummy (Fig. 1.c) showed a
typical clinical sign of smallpox.
Scientists
theorized that the pharaoh died of smallpox
infection. Note the pustular lesion on the face of the
mummy. The lesions are much like that of the more
recent cases of smallpox infection.
Fig. 1.c The face of mummified Ramses V
Around 1000 BCE, in China, smallpox
infection was endemic. They noticed that people
who survived the infection did not succumbed to
subsequent infection following another outbreak.
Chinese folk doctors developed
variolation.
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Variolation involved inhalation of the dried crusts
from smallpox lesions. Later modifications were
done wherein pus from a lesion is inoculated into a
scratch on the forearm of a child.
In the turn of the eighteenth century, English
doctor named Edward Jenner observed that
milkmaids tend to catch “pox” presumably from
cows. These milkmaids were spared from the
devastating effects of smallpox. Thus on May 14,
1796, Jenner obtained infected material from the
hand of a milkmaid named Sarah Nemes and
injected the material into an 8 years old boy named
James Phipps. The boy soon developed fever.
On the 1st of July 1796, Jenner challenged the boy
by deliberately injecting him an inocula coming
from a real smallpox case. As Jenner hypothesized,
the boy did not show any symptom of the disease.
The boy instead developed immunity against the
disease.
Thus, the word vaccination came into being.
Vaccination came from the word “vacca”, which
means cow, where the organism for the first inocula
came from.
A great rush occurred in the clinic of Jenner.
Everybody wanted to be safe from small pox
infection and had their vaccination. Due to the
findings of Jenner and his practice of vaccination,
he is now recognized to be the father of virology
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although he did not know or seen the real causative
agent of the disease.
In the 1800’s, the recognition of
microorganisms as causative agents was first noted.
Two important scientists namely: Louis Pasteur
and Robert Koch, jointly proposed the germ theory
of disease. The theory states that specific organism
cause specific disease. The time of Pasteur and
Koch is known as the golden age of microbiology
yet viruses were elusive.
Koch’s postulate clearly identifies the
causative agent of the disease when:
1. the agent is present in every case of the
disease;
2. the agent can be isolated and grown in vitro;
3. the disease must be reproduced when a pure
culture of the agent is injected into a
susceptible host.
4. The same agent must be obtained from the
experimentally infected host.
Pasteur on the other hand, worked extensively
on rabies. He identified the causative agent as a
virus (the Latin word for poison).
A major distinction must have to be
established since poisons do not multiply inside the
body but viruses do.
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On 12th February 1892, in the St. Petersburg
Academy of Science, Dmitri Ivanowski, a Russian
botanist, presented a paper which showed that
extracts from diseased tobacco plants could transmit
disease to healthy plants after passage through
ceramic filters fine enough to retain the smallest
known bacteria. This is generally recognized as the
beginning of Virology. Unfortunately, Ivanowski
did not fully realize the significance of these results.
The word filterable came into being, thus viruses
were then termed as “filterable agents”.
A few years later, Martinus Beijerinick
(1898) confirmed and extended Ivanowski's results
on tobacco mosaic virus. This was the first to the
development of the modern idea of the virus. He
referred viruses to be “contagium vivum fluidum”
('soluble living germ').
Also in 1898, Freidrich Loeffler and Paul
Frosch showed that a similar agent was responsible
for foot-and-mouth disease in cattle. Thus these new
agents caused disease in animals as well as plants.
In spite of these findings, there was resistance to the
idea that these mysterious agents might have
anything to do with human diseases.
Landsteiner & Popper (1909), showed that
poliomyelitis was caused by a 'filterable agent' - the
first human disease to be recognized as having a
viral cause.
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Frederick Twort (in 1915) & Felix
d'Herelle (in 1917) were the first to recognize
viruses which infect bacteria. d'Herelle called them
bacteriophages (eaters of bacteria).
Louis Pasteur began studies of rabies in
animals in 1881. He was able to develop methods of
producing attenuated virus preparations. He
inoculated rabbits with the virus, then progressively
dry the spinal cords of rabbits. The spinal chord
was then inoculated to healthy animals. The animals
developed immunity against the virus. This was the
first artificially produced vaccine against a virus.
During the Spanish-American War of the
late 19th century along with the subsequent building
of the Panama Canal, American deaths due to
yellow fever were very enormous. The disease also
appeared to be spreading slowly northward into the
continental United States. Through experimental
transmission to mice, Walter Reed, in 1900,
demonstrated that yellow fever is caused by a virus;
the virus is being transmitted by mosquitoes.
In the years that followed, several scientists
exerted efforts to learn more about viruses. The
table below lists some of them and their
contributions to the development in the field of
virology.
In the table below lists some of the scientists
and their contributions in the field of virology.
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Table 1. Scientists and their contribution
Scientist
Year
Contribution
Rous
Shope
Smith, et al
1911
1933
1933
Stanley
1934
Elford
1938
E. Ruska
1939
Kausche, et al
1939
Delbruck
1940
Enders, et al
1949
Hershey and
Chase
1952
Zinder and
Lederberg
Schaffer and
Schwerdt
Tsugita, et al
1952
Avian sarcoma virus
Mammalian cancer
Isolated human influenza
virus
Isolated pure crystalline
TMV
Comparative data on sizes
of viruses
Developed the electron
microscope
TMV visualized using the
electron microscope
Replicative cycle of
bacteriophage
Developed human cell
culture for polio virus
Showed that DNA of
bacteriophage is
infectious
Transduction discovered
1955
Poliovirus crystallized
1960
Established the amino
acid sequence of TMV
coat
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Scientist
Caspar and
Klug
Year
1962
Gammatos
and Tamm
Temin and
Baltimore
Poiesz,et al
1963
Kleid, et al
1981
1970
1980
Barre1983
Sinoussi, et al/
Montagnier
Wang, et al
1986
Contribution
Established the
icosahedral structure of
isometric viruses
Occurrence of double
stranded RNA viruses
Reverse transcriptase
enzyme
Human retrovirus
associated with leukemia
FMD vaccine using
recombinant DNA
technology
Isolation of lentivirus
associated with AIDS
Viroid like structure of
hepatitis delta virus
c. Definition of Terms
CAPSID The protein coat that surrounds the
nucleic acid of a virus.
CAPSOMERS Substructures of virus particles.
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Composed of aggregates of polypeptide
chains that interact to form the basic
structural units of the capsid.
CASE FATALITY RATE (=CFR) The
proportion of clinically apparent cases
which result in death.
CYTOPATHIC EFFECT (=CPE) CPE
consists of morphologic alterations of host
cells, may result in cell death.
ENVELOPE A host-cell-derived membrane,
containing virus specific antigens, that is
acquired during virus maturation.
FOMITE An object (e.g. furniture, book) that
is not harmful in itself but which can harbor
pathogenic organisms and thus may be
involved in transmission of an infection
ICOSAHEDRON A geometric figure
composed of 12 vertices, 20 triangular faces
and 30 edges.
INCLUSION BODIES Usually sites of virus
synthesis or assembly; may be of diagnostic
value (e.g. Negri bodies in rabies infection).
NANOMETER 10-9meter. 1nm = 10Å.
1000nm = 1µm.
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NUCLEOCAPSID The virus structure
composed of the nucleic acid surrounded by
the capsid.
MONOLAYER Sheet of cells forming a
continuous layer one cell thick on a solid
(e.g. glass or plastic) surface. Cells may be
e.g. fibroblast, epithelial, epitheliod in
nature. They may exist in either primary or
continuous (transformed) state.
PEPLOMERS also known as spikes (peplos =
envelope).
PLAQUE A defined area of cell destruction
resulting from virus infection in vitro.
PLAQUE FORMING UNIT (=PFU) A
measure of infectious virus particles. One
plaque forming unit is equivalent to one
infectious virus particle.
POCK A discrete pustular lesion found in the
chorioallantoic membrane or skin following
infection with certain viruses.
PRIONS- are rather ill-defined infectious agents
believed to consist of a single type of protein
molecule with no nucleic acid component.
Confusion arises from the fact that the prion
protein & the gene which encodes it are also
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found in normal 'uninfected' cells. These
agents are associated with diseases such as
Creutzfeldt-Jakob disease in humans,
scrapie in sheep & bovine spongiform
encephalopathy (BSE) in cattle.
SPIKES Surface projection of varying lengths
spaced at regular intervals on the viral
envelope, also called peplomers. Consist of
viral glycoproteins
STRUCTURAL PROTEINS Those proteins
which are present in the virion.
SYNCYTIUM A multinucleated protoplasmic
mass formed by the fusion of originally
separate cells
VIRAL HEMAGGLUTININ A virally coded
protein on the outer surface of some viruses
which reacts with a surface determinant on
red cells. Since such a virion will have many
copies of the surface hemagglutinin, it can
bind to more than one red blood cell, thus
causing hemagglutination.
VIRAL INFECTIOUS DOSE The amount of
virus required to cause a demonstrable
infection in 50% of the inoculated animals
(ID50) or tissue culture cells (TCID50).
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VIREMIA Presence of virus particles in the
blood
VIRION The mature virus particle, with all of
its structural components intact.
VIROID – small, circular RNA molecules with
a rod-like secondary structure, possess no
capsid or envelope and are associated with
certain plant diseases. Their replication
strategy is like that of ordinary viruses.
VIRUS
A small, obligate intracellular parasite
that depends on a living host cell for energy,
precursors, enzymes, and ribosomes to
multiply. It consists of a single type of
nucleic acid, either DNA or RNA, and a
protein coat surrounding the nucleic acid. In
addition, some viruses have an envelope.
VIROSOIDS – also called satellite viruses,
somewhat larger than viroids , they are
dependent on the presence of virus
replication for multiplication (hence
'satellite'), they are packaged into virus
capsids as passengers.
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Name:_________________________________
Questions:
1. Identify who among the scientists named in
the chapter won a Nobel Prize for his
research.
2. Outline the process by which Beijerinck
discovered that TMV is “filterable”
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3. Write an anecdote on the worst viral
infection that you had experienced?
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