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Unit 2 Viruses: Structure
Unit 2 Viruses: Structure
Structure
2.0 Objectives
2.1 Introduction
2.2 Discovery of Viruses
2.2.1 Nature of Viruses
2.2.2 Definition of Viruses
2.2.3 Morphology of Viruses
2.2.4 Morphology of Bacteriophage
2.2.5 Multiplication/Replication
2.2.6 Cultivation of Viruses
2.2.7 Transmission of Viruses
2.2.8 Inclusion Bodies
2.2.9 Virus Mutations
2.2.10 Host Specificity
2.3 Classification of Viruses
2.3.1 Disease Producing DNA Viruses
2.3.2 Disease Producing RNA Viruses
2.3.3 Hepatitis Viruses
2.3.4 HIV and AIDS
2.4 Control of Viral Diseases
2.5 Let Us Sum Up
2.6 Key Words
2.7 Answers to Check Your Progress
2.0 OBJECTIVES
After studying this unit, you should be able to:
l define virus;
l learn the historical background of viruses;
l state the nature and morphology of viruses;
l describe how the virus multiplies in the host cell;
l differentiate between virus and bacteriophage;
l explain the methods of cultivating and transmitting viruses;
l define inclusion bodies, viral mutations and host specificity;
l classify viruses;
l list the important DNA and RNA viruses and the diseases caused by them;
l learn the different types of viral hepatitis;
l discuss HIV and AIDS in humans; and
l explain how viral diseases can be controlled.
2.1 INTRODUCTION
Viruses form a very important group of obligate intracellular living organisms, the structure
of which can only be studied under electron microscope. Often when the doctor is not quite
sure what is wrong with the patient, he says “probably it is virus” and he is probably right
because, with the development of new improved techniques a large number of new viruses 17
Microbiology-II causing one disease or the other have been detected, isolated and identified. Diseases such
as polio, mumps, rabies, herpes, chicken pox, small pox, dengue fever, hepatitis B, etc. are
all caused by one or the other type of virus. The life threatening very serious disease AIDS
with almost 100% fatality rate is also caused by a virus. There are many viruses, which
may cause even the host cell to multiply causing tumours or cancers. Since viruses are
obligate parasites, one may think that all viruses are pathogenic but it is not so. There are
many viruses, which may develop host guest relationship with the host. In other words, the
virus may simply stay inside the host cell as a guest. It may neither benefit nor harm the
cell. Such viruses are called temperate or lysogenic phages.
In this unit, you will learn the definition, discovery, nature, structure and reproduction in
viruses. You will also study their cultivation, transmission, mutation, host specificity,
inclusion bodies, classification and types of bacteriophages. You will also become familiar
with some of the well known viral diseases caused by DNA or RNA viruses. We shall also
discuss hepatitis viruses and some of the rapidly rising severe and life threatening
infections such as AIDS (Acquired Immuno Deficiency Syndrome) and PGL (Persistent
Generalized Lymph Adenopathy). In the end, the role of antibiotics/drugs and vaccines in
the prevention of viral disease is also included.
By the late 1800, Louis Pasteur, Robert Koch and other pioneer bacteriologists had
demonstrated that many diseases in man and other organisms were caused by bacteria.
Some diseases puzzled them because they could find no bacteria or other organisms that
were responsible for the disease symptoms. One such disease was tobacco mosaic disease
(TMD) occurring in tobacco plants. In 1892, a Russian biologist Iwanowski was the first
one to find out that the causative agent of TMD was a filterable tobacco mosiac virus
(TMV) which could be transmitted from an infected organism to a healthy organism of the
same kind. After this, scores of viral diseases of plants were known. In 1898, Beijerinick, a
Dutch microbiologist, confirmed the work of Iwanowski and described the cause of
infection in tobacco plant as ‘Contagium Vivum Fluidum’, Latin words, meaning ‘living
fluid infectants’ or ‘living infectious fluid’.
In 1900, Walter Reed with his co-workers discovered the virus of yellow fever, the first
viral disease of man. After that a large number of human viruses have been known and
isolated.
Viruses that attack bacteria were first observed in 1915 by a British Scientist Twort. Later
in 1917, French investigator d’Heralle fully studied these bacterial viruses and named them
as ‘bacteriophages’ or ‘phages.’
The year 1935 was very important year in the field of virology. It is in this year, that
electron microscope had been constructed which could magnify as much as 300,000 times
and W.M. Stanley an American Microbiologist studied TMV under electron microscope.
Stanley in 1946 isolated TMV from the host cell and was awarded noble prize for his
wonderful work.
Living Characters
i) They reproduce only in living cells.
ii) They have the capacity for growth in size and numbers.
iii) They undergo mutations of their genes and as in living; they also have the ability to
undergo changes in hereditary characters.
iv) They can adapt themselves to their environment through natural selection.
Thus, we can say that although viruses seem to be almost on the border line between living
and non-living, the two characters of living viz. mutations and their adaptation through
natural selection are not known anywhere outside living things. Therefore, it seems
reasonable to classify viruses as living ones, though they are very primitive and do not
exhibit all the characters found in other forms of living matter.
1) Size
All viruses are extremely small and cannot be seen with a compound microscope. The
following three basic techniques are used to determine the size of virus:
a) Filteration through graded membrane;
b) High speed centrifugation;
c) Direct observation under Electron Microscope.
Viruses are measured in millimicrons (mµ, one millimicron is 1000th of a micron) and vary
considerably in size. The size ranges from 15 mµ to 450 mµ. The smallest virus is of a foot
and mouth disease of cattle (15 mµ) and the largest virus is of a parrot fever (450 mµ). In
humans, the smallest virus is of yellow fever (20 mµ) and the largest virus is pox virus (400
mµ).
2) Shape
Viruses, like other microorganisms, vary in shape. The shape remains constant for any
particular kind of virus but varies from one type of virus to another. These may be
spherical, rod shaped, cuboidal, rhomboidal (multisided), needle shaped etc. Rabies virus is
bullet shaped, TMV is rod shaped, polio virus is spherical, pox virus is rectangular or brick
shaped. Some viruses are irregular in shape. Bacteriophages have head and tail like sperms
(virus of bacteria is called bacteriophage or phage, sub-section 2.2.4).
3) Structure
Viruses have a relatively simple structure as compared to other living things. Virus particle
is called virion, which consists of two parts viz. the central core or nucleic acid core and
protein coat. 19
Microbiology-II The Central Core or Nucleic Acid Core: It may be either ribonucleic acid (RNA) or deoxy
ribo-nucleic acid (DNA). Plant viruses contain RNA while animal viruses have DNA or
RNA. The two together are never found in a virus.
The Protein Coat: The protein coat covers the central core and is called capsid. The capsid
itself is formed of a number of subunits known as capsomeres. Some viruses are
surrounded by an envelope which is lipoprotein in nature as seen in herpes virus, pox virus,
rabies virus etc.
Envelope may have protein subunits, projecting on its surface which are called peplomeres.
A virus may have more than one type of peplomere as in Influenza virus which contain two
types of peplomeres [see Fig. 2.1(a)&(b)]. If there is no envelope surrounding the virion, it
is called as naked virion.
Capsid
RNA
Capsomeres
Envelope
Peplomeres
DNA
Capsid
Capsomeres
1) Structure
Bacteriophage has two distinct parts, namely, hexagonal head and a cylindrical tail. The
head in its central portion contains DNA surrounded by a protein coat or capsid. The tail
consists of a hollow tube surrounded by a contractile sheath. The tail at its base has a base
plate which is connected with six long thin tail fibres. The most extensively studied group
of bacteriophage is T series that invade the non-motile strain of Eschierichia coli. T series
bacteriophages are of fairly large size and easy to culture and purify (Fig. 2.2).
Head
DNA
Protein coat
Demarcation between
head and tail
Tail
Sheath
Base plate
Tail Fibres
Temperate or Avirulent Type: These are also called as lysogenic bacteriophages. These are
the bacteriophages in which the infection is not apparent. They do not infect the host cells.
These simply persist indefinitely in the host cells in a quiescent state.
2.2.5 Multiplication/Replication
For understanding how these viruses cause diseases in their hosts, let us now learn how
they enter the host cells and multiply.
Viruses multiply by a much more complex process than binary fission. They do not
reproduce in inanimate media, but they can be grown by inoculation into animals,
embryonated eggs or tissue cultures. They lack the machinery to synthesize their own
proteins; instead, they synthesize their proteins from the machinery of the host cell. The
phenomenon of viral multiplication was first studied in bacteria and later in animal cells.
Although the pattern of multiplication in bacteria and animal viruses is more or less
similar, there are also important differences.
1) Animal Inoculation
It is one of the oldest methods for the growth of viruses. In this method, animals are
inoculated with virus. The virus grows in these animals in the form of a disease.
23
Microbiology-II Table 2.2: Disease Producing RNA Viruses
i) Poliomyelitis Viruses
ii) Rhino Viruses
iii) Orthomyxo Viruses (Influenza Viruses)
iv) Paramyxo Viruses
1) Mumps Virus (Rabula inflans)
2) Measles Virus (Rubeola or Morbilli)
3) Parainfluenza Viruses
v) Rhabdo Viruses (Rabies Viruses)
vi) German Measle Viruses (Rubella Viruses)
vii) Arbo Viruses (Arthropod Borne Viruses)
a) Mosquito Borne Arbo Viruses
1) Chikungunya Viruses
2) JBE Viruses (Japanese B Encephalitis Viruses)
3) Yellow Fever Viruses
4) Dengue Fever Viruses
b) Tick Borne Arboviruses
KFD Viruses (Kyasanur Forest Disease Viruses)
viii) Corona Viruses
ix) Rota Viruses
x) Retro Viruses (Oncogenic or Tumour Producing RNA Viruses)
a) HTLV (Human T cell Leukemia Viruses HTLV-1 and HTLV-2)
b) HIV (Human Immuno Deficiency Virus HIV-1 and HIV-2)
a) Pox Viruses
Lateral Body
Outer Coat
Lateral Body
Chicken Pox: Chicken pox is one of the commonest childhood infections and it may
occur at any age. The incubation period varies 2 to 3 weeks. It is transmitted by
coughing or sneezing or by direct contact with the patient. The vesicles are
surrounded by red rim. There are rarely depressed scars as seen in small pox. If the
infection is severe it may lead to complications such as haemorrhagic eruption,
leukaemia, viral pneumonia, encephalitis etc.
iv) Adeno Viruses: The name is derived from the fact that they were first found in
adenoid tissue removed by surgical operations. They multiply in nucleus and have
no envelope. They enter through the respiratory tract and exit through the
respiratory secretions. The adenoviruses have more than thirty three serotypes and
type 12, 18, 31 can cause tumours in humans. The diseases produced by adeno
viruses are pharyngitis, pneumonia, acute respiratory disease and pharyngo-
conjunctival fever. Sometimes they infect the eye to cause mild conjunctivitis.
Transmission is through nasopharyngeal secretion or sputum of saliva or through
physical contact or droplets.
v) Human Parvo Viruses: They are small and simplest DNA viruses without
envelope. They often cause disease in animals. Parvo-virus B-19 is the only one
which infects humans. The first human parvo-virus was discovered by Paver in
1973 in stool specimens. The second was found in the serum of blood donors and a
third type was recovered from human tissue.
vi) Papova, Polyoma and Papilloma Viruses: They are small DNA tumour producing
viruses which cause a variety of tumours in different parts of the human body.
vii) Cytomegalo Virus (CMV): It was first reported in the early years of 20th century.
The virus is present in saliva, urine, semen, uterine cervix, blood and human milk.
It can spread through saliva or by inhalation or sexual intercourse. It is a source
of cytomegalo inclusions disease but it can also cause tumours.
viii) Epstein Barr Virus (EB): It was first reported in 1964 in African children. It
causes tumour in jaw. Infection occurs through respiratory tract by close contact
with patients. The common mode of infection is believed to be by kissing; hence the
25
Microbiology-II disease is also known as kissing disease. It is characterised by sore throat and
presence of abnormal lymphocytes in the peripheral blood.
ix) Hepatitis B Virus (HBV): It is a DNA virus and can cause carcinoma in humans
(see details in sub-section 2.3.3).
i) Poliomyelitis Viruses
These are smallest spherical viruses present in the cytoplasm of infected cells and cause
poliomyelitis (Infantile paralysis) disease. There are three distinct types of poliomyelitis
viruses (Type I, II and III) and each type includes a number of strains. Type I is the
commonest and responsible for the epidemic. These viruses can survive in faeces for
several weeks. Faeces of patient and carrier is the important source of polio virus. The
disease spreads through contaminated drinking water, sewage etc.
Its principal portal of entry is the gastrointestinal tract via mouth. These viruses multiply in
the mucous membrane of the pharynx and intestine and then spread to the blood and finally
reach the nervous system. They cause inflammation of the spinal cord, damage motor cells
and the motor responses to the affected parts are weakend or destroyed. The incubation
period is about ten days with range from 4 days to 4 weeks. Two types of vaccines viz.
Sabin’s live polio vaccines and Salk’s killed polio vaccines are available. Salk’s vaccine is
given by injection and Sabin’s vaccine is given orally. Sabin’s vaccine is economical and
single oral dose gives life long immunity. Salk’s vaccine is given by injection in 2 or 3
doses and it is followed by booster doses.
Poliomyelitis is world wide in distribution. Originally the position of polio disease was
similar in all countries but now in advanced countries it is almost eradicated and in
developing countries including India, immunization has brought down the incidence. In
India all steps are being taken to eradicate polio disease from every part of the country.
ii) Rhinoviruses
Rhino means nose. They are so named because of their special adaptation to grow in the
nose. There are at least more than 100 serotypes of Rhinoviruses. Because of so many
serotypes, it has not been possible to make ideal efficient composite vaccine. They are
responsible for the common cold. The disease is trasmitted by droplets. The incubation
period is 2 days. Human is the only natural host of rhinovirus.
Spikes
RNA
Protein coat
Envelope
Neuraminidase
Spikes
RNA
Protein coat
Envelope
3) Parainfluenza Viruses
They are classified into 4 types: parainfluenza types 1-4. Type 3 causes lower respiratory
tract infections (bronchitis, bronchiolitis) while type 4 causes minor respiratory infection.
Type 1 and 2 cause severe infections.
v) Rhabdo Viruses
The term rabies is derived from the Latin word “Rabidus” meaning “Mad”. These viruses
are bullet shaped and multiply in neuroplasm but at times these also multiply in salivary
glands. It is surrounded by lipoprotien envelope from which project spikes. In infected
brain the characteristics cell inclusions known as negri bodies are present in the
nucleoplasm. Rhabdo virus causes the disease rabies also called hydrophobia because the 27
Microbiology-II patient shows fear of water and is unable to drink in spite of being very thirsty. The
incubation period varies from 1 to 3 months though it may be as short as 10 days or as long
as 3 years. The incubation period depends upon the site of the wound and its distance from
the brain. If the site of the wound is near the brain the incubation period will be fairly
short. The disease is transmitted chiefly through the saliva of rabies dog. Humans are
infected by the bite of a rabid dog or any other rabid mammal and the virus spreads from
the wound through the nerve fibre to the central nervous system (brain and spinal cord).
From central nervous system virus spreads to salivary glands and other tissues.
Spikes
Protein coat
Envelope
RNA
The disease is characterised by depression, itching at the site of primary infection, fever,
paralysis of the face muscles, eyes and tongue and then spreads to the limbs. Fear of water
is the dominant symptom which leads to convulsions, coma and death. Since the virus is in
the saliva, precautions must be taken to prevent its entrance into cuts and scratches. Human
rabies can be checked by vaccination of pets and destruction of stray animals. Brain of
suspected animal should be examined for negri bodies. Failure to find negri bodies does
not exclude the possibility of rabies. If there is any doubt, anti-rabies injections should be
given before symptoms appear.
Neuroplasm
Nerve cell
Fig. 2.6(b): Large nerve cell from human brain showing Negri bodies
Activity 1
1) Examine the stained slide of brain of rabid dog or any other rabid mammal in the
nearby laboratory and look for the negri bodies.
2) If a person has been bitten by a dog, suspected to be rabid, what will be your
contribution or advice as a nurse to him?
28
vi) Rubella Virus (German Measle Virus) Viruses
Rubella virus causes German measles. It is surrounded by an envelope with spikes, on its
surface. It is not so highly infective as measles but it has a tendency to develop
complications. The virus is inhaled and grows in mouth and throat and small white patches
are seen in the mucous membrane of the upper respiratory tract. After the incubation period
(16 to 18 days), the patient develops fever and skin shows blood rashes. The virus may also
spread up to middle ear and attack lymph glands. Arthritis is common complication
especially in females. The infection may be transmitted by the pregnant mother to the
foetus and the foetal cells may be damaged. The foetus may die or develop some serious
heart abnormalities, large liver, large spleen, etc. It is transmitted by nasopharyngeal
secretions borne in the air or dust.
RNA
Envelope
x) Retro Viruses
Two types of retro viruses viz., Human Tcell Leukemia Virus (HTLV) and human immuno
deficiency virus (HIV) are responsible for causing human diseases. At present there are
two strains of HTLV, viz. HTLV-1 and HTLV-2 which have been isolated and both are
basically similar. They are enveloped viruses that develop by budding through the host cell
membrane and cause leukemia disease, a type of blood cancer formed by the excessive
growth of leucocytes. They are usually transmitted from mother to the child. HIV also has
two strains HIV-1 and HIV-2 giving rise to slowly developing disease AIDS. We will
discuss this disease separately under the title HIV and AIDS (see sub-section 2.3.4).
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3) Distinguish between Rubella and Rubeola virus.
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4) How are Dengue Fever Viruses transmitted from one individual to another?
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5) Name two types of Retroviruses causing human diseases.
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Hepatitis A virus
Tubular
Shelled spherical
Spherical
Organisms have been found in various body fluids such as saliva, menstrual and vaginal
discharges, seminal fluid and breast milk. These are rarely seen in urine, bile, faeces, sweat
and tears. Hepatitis B vaccine is now available for prevention against hepatitis B.
32
2.3.4 HIV and AIDS Viruses
HIV (Human Immuno Deficiency Virus) belongs to retrovirus group of RNA viruses. At
present there are two strains of HIV known as HIV-1 and HIV-2 originated from Central
Africa and West Africa respectively. Both these strains of HIV cause the life threatening
disease Acquired Immuno Deficiency Syndrome (AIDS) which is of a very serious type
and often fatal. The fatality rate for AIDS is very high reaching 100% in some countries.
There is yet no cure for AIDS. A lot of research work is going on in this field of virology
and scientists are busy in the development of vaccine against HIV. Until treatment and
vaccines are available, urgent programmes need to be devised with regard to public health,
social and sexual behaviour.
1) History
AIDS was first recognized as a disease in USA (New York and Los Angeles) in 1981 in
homosexuals and drug addicts who suffered either from pneumocystis carinii pneumonia or
from Kaposis Sarcoma (KS) disease. In 1984, Dr. Robert Gallo isolated HIV from AIDS
patients in National Institute of Health, USA and stated that under electron microscope it
exhibits characteristic exotic flower appearance.
In India, AIDS was first discovered in 1985 among six heterosexuals in Tamil Nadu. Since
then it has spread to every part of India at an extremely rapid rate and the highest ever
documented rate of HIV spread in the world was in Pune, India. In 1996, it was soon
established that there were more new HIV cases in South Asia than any other region in the
world. The number is rapidly increasing every year and it is estimated that in the next few
years India will have 20-50 million people infected with HIV.
3) Mode of Infection
AIDS is a communicable disease but it is much different from other communicable viral
diseases of human beings. AIDS can be caused only if HIV enters the blood stream of
human blood. There are four main modes of spread. These are through
a) sexual intercourse among homosexuals and heterosexuals;
b) infected blood and blood products (blood transfusion);
c) infected needles, syringes and surgical instruments; and
d) infected mother to her newborn baby through breast milk.
Whether it can spread by contact with large amounts of infected saliva is not known as
saliva has natural compounds that inhibits HIV infection.
HIV does not spread through casual contact such as sharing food utensils, towels, beddings,
telephones or toilet seats. Also, it does not spread by insects like mosquitoes, flies or bed
bugs.
4) Structure of HIV
HIV under electron microscope appears like an exotic flower. It is a mature virion, the central
part containing two identical copies of viral ribonucleic acid (RNA), which is unusual
among viruses. RNA is surrounded by a protein coat with two proteins (P 17/18 and P24/25) 33
Microbiology-II
Protein coat P17/18
Envelope
GP 41
RNA
GP 120
and an envelope with projecting spikes. The envelope is rich in glycoproteins (GP41, GP 120
and GP 160). When the virus enters the cell, first the outermost envelope is lost at the site of
entry, then the protein coat is also cast off and RNA starts replicating in the cell and thus a
large number of virions are formed in the cell.
Ultimately the cell dies and newly formed virions bud out through the cell membrane and
infect fresh cells. These virions suppress the body’s immune system by killing T4 cells and
an unusual neoplasm develops resulting in skin rashes, fatigue, fever, weight loss,
breathing problems, chronic diarrhoea, white patches on tongue, oral candidiasis,
lymphadenopathy and finally AIDS disease.
Earlier, it was believed that, since viruses used the protein synthesizing machinery of the
34 host cell to synthesize their proteins, their replication could not be inhibited without
damaging the host cell. But now, with the development of new genetic techniques and Viruses
technologies, vaccine strains can be produced with the desired antigenic characters and
the viral infection may be checked by attacking virus at special areas without damaging
the cell.
i) Control of viral diseases by antibiotics and chemotherapeutic agents: Viruses
are not susceptible to antibiotics or chemotherapeutic agents. Antibacterial
antibiotics have produced very poor results against viruses. As viruses are
intracellular parasites, any chemical used to inhibit the viral replication also
damages the host cell. Most of these drugs are highly toxic and cannot be used for
human beings. Attempts are being made to synthesize antiviral drugs with low
toxicity and some degree of success has already been achieved in few cases. Anti-
AIDS drugs such as Zidovudine and Lamivudine are now available for AIDS. These
are given, in cases of needle stick injury or unprotected sex, three times daily for
one month starting within forty eight hours.
ii) Control of viral diseases by vaccines/vaccination: Vaccination, unlike the use of
drugs, is the simplest and safest method to prevent viral diseases. Edward Jenner
was the first one who in 1798 gave the idea of live organisms as vaccines. He
developed cowpox vaccine against small pox in human beings. Since then many
vaccines have been produced from living or killed microorganisms to prevent viral
diseases. By using such effective vaccines great success has been achieved in
controlling small pox and polio and there is a huge decline of several other viral
diseases such as yellow fever, measles, mumps etc. Now-a-days, vaccine is also
available for the dreaded disease, e.g. Hepatitis B, but unfortunately no vaccine has
yet been made for the most dangerous disease AIDS.
1) The two characters of living viz. mutation and adaptation through natural selection are
not known anywhere outside living things. Therefore, it seems reasonable to consider
virus as living even though they are primitive and do not exhibit all the characters found
in living things.
2) Virion is a complete mature particle.
3) Capsomeres are subunits of the protein coat.
37