VIROLOGY

Study of viruses and virus-like

agents

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 Outline
• Brief history
• Overview of virus
• Structure of viruses
• Nucleic acid
• Capsid
• Envelope
• receptors
• Classification of viruses
• Comparison between viruses and cells
• Virus host interactions
• Viral replication
• Bacteriophages
• Prions
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 Discovery
• First discovered at the end of the 19th century and evidence was based on the
earliest symptoms of poliomyelitis.
• Symptoms of viral diseases were identified earlier
• Infectious diseases rabies could not be explained by the bacteria theory
• Unlike bacteria, ‘this organism’ could not be retained by filters like bacteria and were
referred to as ‘filterable agents’.
• The chemical nature of viruses was their identifiable features until the 1940s
when the electron microscope was invented.
• Golden age saw the usage of electron microscope to observe the virus and the
development of cell tissue culture
• Several viruses have been isolated, their structure identified, replication patterns studied
and understood.
• This has led to the development of effective antiviral therapy and vaccines3
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 What is virus?
• Acellular ,Sub-microscopic (20 - 750 nm); cannot be viewed under the light
microscope

• Obligate intracellular
• Incapable of replication unless occupying a living cell

• They possess the nucleic acid DNA or RNA (never both) in a protein coat,
capsid.

• Resistant to antibiotics but may be inhibited by antiviral agents

• In simple terms: an infective agent that typically consists of a nucleic acid

molecule in a protein coat (capsid), is too small to be seen by light microscopy,
and02/25/2023
is able to multiply only within the living cells of a host. 4
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 Structure of virus
• Viruses vary in their sizes and shapes but the general structure consists of;
• Nucleic acid: DNA or RNA
• Capsid – a protective protein coat
• Envelope –outer lipoprotein membrane
• Nonstructural proteins

• They vary largely in their general structure.

• Differences account for the high diversity of viruses and the differences in
their properties.
• Resistance to antiviral drugs and viricidal agents
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 Source: https://www.thoughtco.com/dna-
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Viral Nucleic acid
• Genome is composed of either RNA or DNA (never both)

• It can be;
• Double stranded (ds) or single - stranded (ss)
• Linear (e.g. poliovirus) or circular (e.g. hepatitis B virus)
• Contains several segments (e.g. influenza— eight segments of ss RNA) or one molecule
(e.g. poliovirus).

• Based on the nucleic acid content, viruses can be distinguished into 6 groups
(groups will be attached to notes)

• Nature of nucleic acid is an important indicator of how effective an antiviral

treatment will be.
• Eg. Retroviridae (eg is HIV) need a special enzyme, reverse transcriptase during
replication and it is a primary target for antiretroviral
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Viral capsid
• Capsid protects the genome material from physical and chemical damage
such as in disinfection.

• Composed of subunits known as capsomeres.

• Nature and association of capsomeres give capsid its shape and also provide
resistance to chemical and physical agents

• The assembly of the capsomeres results in two different architectural styles;

icosahedral and helical symmetries.
• Other complex structures can be found in other viruses such as mammalian and
bacterial viruses
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• Viruses with an icosahedral capsid usually have capsomeres in the form
of pentons and hexons and the number varies considerably between
viruses.
• Example is adenovirus; consists of 240 hexons and 12 pentons and the poliovirus;
consists of 20 hexons and 12 pentons, forming a much smaller structure.

• Viruses with a helical capsid have their subunits symmetrically packed in

a helical array, appearing like coils of wound rope under electron
microscopy. (e.g. influenza and mumps viruses).
• Though the core of these viruses are hollow, the nucleic acid does not fill the
hollow. It is embedded into ridges on the inside of each capsomere

• Damage is caused to the nucleic acid after disintegration of the capsid due
to chemical or physical damage.
• This is because there is a close association between nucleic acid and capsid protein
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 Icosahedral symmetry

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 Complex structures
Head consists of an icosahedral shell
attached via a collar to a helical tail.

At the end of the tail is a plate which

functions in attachment to the bacterial
host.

In addition thin protein fibres are

attached to the plate, again involved in
binding to host.

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 Viral Envelope
• It is a lipidic structure that surrounds the viral capsid and originates from the host
cell.

• The envelope can come from the host cell nuclear membrane (e.g. herpes simplex
virus) or the cytoplasmic membrane (e.g. influenza virus).

• The envelope is added during the replication process or following excision of the
viral progeny from the host cells.

• Though envelope is from host cell, host proteins are absent. The proteins are
encoded by the viral genome

• Enveloped viruses are generally considered to be the most susceptible to chemical

and physical conditions
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 Viral receptors
• Glycoproteins can be found usually protruding from the viral capsid
or embedded in the envelope

• Are important for viral infectivity as they recognize the host cell
receptor site conveying viral specificity

• In bacteriophages, these structures can take the shape of tail fibres.

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 Classification of viruses
• Morphology: virion size and shape, presence or absence of peplomers or
envelopes etc.

• Physicochemical and physical properties: virion molecular mass, pH stability

etc.

• Genome: type of nucleic acid, size of genome, strandedness, sense etc,

• Biochemical constituents: Proteins, lipids, carbohydrates, etc

• Genome organization and replication: genome organization, strategy of

replication, translational and transcriptional characteristics.

• Biologic Properties: natural host range, mode of transmission, pathogenicity etc.

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 Classification of viruses based on family
ICTV (The International Committee on Taxonomy of Viruses)

• 71 families recognized by ICTV

• 24 human and animal viruses.

• 2 “floating”
(the genera Arterivus and Deliavirus)

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 The Family Picornaviridae
• 28-30nm in diameter, capsomeres arranged in icosahedral symmetry.

• Single stranded RNA.

• Replication and assembly takes place in the cytoplasm and virus is

released via cell destruction.

• Infection is acute and cytolytic, but persistent infection can occur with
some viruses.

• Narrow host range and transmission is horizontal, mainly by contact,

feacal/oral (mostly), or airborne route (in rare cases) .
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• Unstable below pH 7 and stabilized by divalent cations
• Insensitive to ether, chloroform and nonionic detergents.
Examples:
Enterovirus: polioviruses
Rhinovirus: human rhinovirus
Hepatovirus: hepatitis A virus

Aphthovirus: Foot and mouth disease

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 The Family Caliciviridae
•30-38nm in diameter with 32 cup shaped surface depressions and
arranged in icosahedral symmetry
•Single stranded RNA (positive)
•Replication and assembly takes place in the cytoplasm and virus is
released via cell destruction.
•They have narrow host range and insensitive to ether, chloroform and
detergents.

•Some are inactivated, others are enhanced by trypsin.

•Example: Calicivirus: cause gastroenteritis in human.
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 The Family Astroviridae
•28-30nm in diameter and spherical in shape
•Single stranded RNA (positive)
•Have narrow host range and transmission is feacal/oral route.
•Distributed worldwide.
•Thermostable, resistant to acidic pH , ether, chloroform, lipid
solvents, nonionic, anionic and zwitterionic detergents.
•Example: Astrovirus; Causes both human and animal infections.
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 The Family Alphaviridae
• Transmitted by mosquitoes and hematophagous arthropods

• Stable at pH 7-8 (rapidly inactivated at acidic pH)

• Thermolabile and sensitive to organic solvents and detergents.

• Exhibit pH dependent haem agglutinating activity.

• Examples: Alphavirus and Rubivirus (Rubella virus). Rubella virus occurs

worldwide but infects only humans and is transmitted by contact and
aerosols.

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 The Family Flaviviridae
• 45-60nm in diameter and spherical in shape with a lipid envelope.

• Single stranded RNA (positive).

• Has 2-3 membrane-associated proteins and core proteins.

• pH dependent haem agglutinating activity.

• Examples: Flavivirus: causes yellow fever (cytolytic and transmitted by

mosquitoes and ticks)
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 The Family Coronaviridae
• 80-220nm in diameter and very pleomorphic

• Single-stranded RNA (positive)

• Mature in the cytoplasm by budding through the endoplasmic reticulum and Golgi
membranes.

• Narrow host range and are transmitted through aerosol, faecal /oral and fomite

• Sensitive to heat, lipid solvents, nonionic detergents, formaldehyde, and oxidizing

agents.

• Some are stable at pH 3.0.

• Examples:
02/25/2023 Coronavirus and Torovirus. (Common cold and respiratory tract infection
26 ).
 The Family Paramyxoviridae
• 100-300nm in diameter and pleomorphic

• Has a lipid-containing envelope with a coiled helical nucleocapsid.

• Single stranded RNA (negative-sense).

• The surface glycoproteins of some viruses have neuraminidase (genus

Paramyxovirus)

• Paramyxovirus and Mobillivirus genera have haem-agglutinating activity.

• All genera have fusion activity.

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• Narrow host range

• Present in vertebrates, mostly mammals and birds.

• Transmission is mainly by aerosols and droplets.
• Sensitive to heat, lipid solvents, nonionic detergents,
formaldehyde and oxidizing agents.
• Example: Paramyxovirus: human influenza virus 1 & 3
Rubulavirus: mumps virus Morbillivirus: measles virus
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 The Family Orthomyxoviridae
• 80-120nm in diameter and pleomorphic (often spherical)

• Single stranded RNA (negative-sense)

• Virus enzyme include a transcriptase, endonuclease and a receptor destroying

enzyme.

• Transmission among humans is by aerosols and droplets but water-borne among

ducks.

• Sensitive to heat, lipid solvents, nonionic detergents, formaldehyde and oxidizing

agents.

• Exhibit hemagluttinating activity and example include Influenza virus A, B and C.

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 The Family Retroviridae
• 80-100 nm in diameter.

• Spherical (icosahedral) and enveloped.

• Single stranded RNA (positive-sense).

• Associated with many different diseases: leukemia, lymphomas,

sarcomas, carcinomas, immunodeficiencies, etc.

• Sensitive to heat, detergents and formaldehyde and relatively resistant

to UV light.

• Genus include: Spumavirus and Lentivirus (HIV 1 & 2)

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 The Family Herpesviridae
• Pleomorphic but mostly spherical, consist of an envelope and an icosahedral capsid.

• Narrow host range and transmission is usually by contact (saliva, urogenital

excretions or aerosols).

• Some induce neoplasia and most persist for the lifetime of their hosts.

• Sensitive to acid, heat, detergent, organic solvents, and UV and gamma irradiation.

• Subfamily: Alphaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae

• Genus: Simplexvirus, Varicellavirus, Cytomegalovirus

• Causes chicken pox (varicella zoster virus) and herpes simplex infection.
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 The Family Poxviridae

• Large and brick shaped.

• Single molecule of double stranded DNA.

• Transmission is by direct contact, formite, aerosol or arthropods.

• Generally sensitive to detergents and formaldehyde.

• Orthopoxvirus which causes small pox and cowpox infections.

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 The Family Papillomaviridae
• Non-enveloped, DNA.
• Narrow host range.
• Transmitted by contact (sexual contact) and aerosols.
• Resistant to ether, acid and heat.

• Papillomaviruses cause tumours (warts, papillomas, and

carcinomas).
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 Classification Based On Genome
• DNA Viruses • Hepadnaviridae
- dsDNA, envelope, icosahedral, 42 nm
• Poxviridae -Hepatitis B virus
- dsDNA, envelope, complex 300x240x100
nm • Parvoviridae
- Vaccinia virus, Molluscum contagiosum - ssDNA, nonenvelope, icosahedral, 18-26
virus nm
- Adeno-satellite virus, Parvovirus B19
• Herpesviridae
- dsDNA, envelope, icosahedral, 100-150 nm
- Herpes simplex virus type 1, 2, Varicella- • Adenoviridae
zoster - dsDNA, non-envelope, icosahedral, 70-90
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• RNA Viruses • Togaviridae
- ssRNA +, envelope, icosahedral
• Paramyxoviridae - Rubella virus
- ssRNA -, envelope, helical
- Measles virus, Mumps virus • Flaviviridae
- ssRNA +, envelope, icosahedral
• Picornaviridae - Yellow fever virus, Dengue virus
- ssRNA +, nonenvelope, icosahedral
- Rhinovirus, Enterovirus • Bunyaviridae
- ssRNA -, envelope, helical
• Orthomyxoviridae - Hantaan virus
- ssRNA -, envelope, helical
- Influenza virus • Filoviridae
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- ssRNA -, envelope, helical 35
- Ebola virus, Marburgvirus
 Comparison of Viruses and Cells
Property Virus Cell
Nucleic acid DNA or RNA Both DNA and RNA

Proteins Few Many

Lipoprotein membrane Envelope present in some Cell membrane present in all

Ribosomes Absent Present

Mitochondria Absent Present in eukaryotes

Enzymes Few or none Many

Multiplication by binary No Yes (most cells)

fission
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 Virus – host cell interactions
• Viruses need to interact with a host cell as they cannot reproduce on their own.
• On their own they have no metabolism and cannot synthesize their own proteins, lipids or
nucleic acids.

• They are therefore considered as true intracellular parasites that grow within living
cells and use their energy and synthetic machinery to produce viral components.

• When viruses are produced and they exit the host cell, the end result may usually
be cell death though may not be immediate

• Following the replication of one virus within the host cell, hundreds of new viruses
(virus progeny or virions ) can be released and infect adjacent cells (within a
tissue).
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• The propagation from one infected cell to new cells, and the subsequent
destruction of tissue or cells, provides signs of the viral disease.

• There can be some host that serve as reservoirs and carry virus to susceptible
recipients.

• Viruses are usually very specific and rarely cross species barriers in terms of the
host they attack
• There are exceptions such as rabies and influenza that can cause diseases in both animals
and humans

• On the basis of host specificity, three major viral groups can be distinguished:
• (1) viruses of bacteria and blue - green algae
• (2) plant viruses
• (3) animal (including insect) viruses.
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• Viruses can interact with the host cell in five different ways:

• Multiplication of the virus and destruction of the host cell upon release of the
viral progeny

• Multiplication of the virus and release of the virions without the immediate
destruction of the host cell

• Survival of the virus in a latent stage without noticeable changes to the infected
cell

• Survival of the infected cell in a dramatically altered or transformed state (e.g.

transformation of a normal cell to one having the properties of a cancerous cell)

• Incorporation of the viral nucleic acid in the host cell genome without
noticeable changes to the infected cell
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• There is a great diversity in viral infections and viral diseases.

• There the asymptomatic infections where the virus replicates in the host but there is
no symptoms of the disease they cause. Eg…………………….

• Other common infections produce some mild symptoms, such as a low- grade fever
and a ‘runny nose’. Eg…………………

• In other cases, symptoms spring up very quickly following an infection which can
result in even death. Eg……………………………

• Others exhibit a range of symptoms from mild to very severe. Eg……………….

• Others do not cause immediate symptoms but following systematic destruction of the
host cell, the end result is an incurable terminal disease. Eg…………………………
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 Viruses and Cancers
• It is estimated that about 20% of human cancers are caused by viruses

• Virus infected cells acquire characteristics of tumour cells exhibiting uncontrollable

growth

• Examples include:
• Epstein – Barr virus (EBV) has been associated with the formation of lymphomas and
nasopharyngeal carcinomas
• The hepatitis B and C viruses are associated with hepatocellular carcinoma
• Human papilloma viruses are associated with cervical cancer
• Human T - cell lymphotrophic virus type 1 associated with adult T - cell
leukaemia/lymphoma syndrome
• HIV is associated with Kaposi’s sarcoma

• The acquisition of viral genes by the host must be followed by other events such as
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• Cells contain genes called protooncogenes for normal cell replication.

• Their functions are controlled by tumour-suppressor genes.

• Some DNA viruses can encode for proteins that block the function of these
tumour-suppressor genes.
• This makes protooncogene to function as oncogene, and cell division is
allowed to proceed uncontrolled.
• An oncogene is a gene associated with the conversion of a cell to a cancerous
form
• Retroviruses carry their own, altered, version of the cellular oncogene
• Which they integrate into host’s genome, leading to uncontrolled cell growth
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 Viral replication

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 Viral replication
• Viruses multiply in living host and use the energy and synthetic
machinery from host.

• Replication is needed to ensure multiplication of viruses and survival

of its kind
• Formation of identical viral progeny.

• Replication cycle varies greatly as well the time to produce and release
the virions.
• Human viruses have a generally slow cycle, about 4 to 40 hours
• Bacteria viruses have a faster rate usually about 20 mins
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• Knowing how viruses replicates is important for developing new anti-viral
medicines

• Viral replication cycle has been divided into six distinct phases

• Viral attachment to the host cell

• Penetration into the host
• Uncoating of the virus
• Replication of the virus
• Assembly of the virion
• Release of the virion
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 Attachment
• Viruses attach to the host cell membrane through the glycoproteins
embedded in the viral envelope or proteins found in the capsid

• These structures recognize and bind receptors on the host cell and provide
the virus with its high specificity

• Viral attachment to the cell surface can be divided into three phases:
• An initial contact mainly dependent on Brownian motion
• A reversible phase during which electrostatic repulsion is reduced and
• Irreversible changes in virus- receptor– host- receptor configuration that initiates
viral penetration through the cell membrane.
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 Penetration of the viral particle
• Three major mechanisms are responsible for viral penetration through the cell membrane
• Endocytosis
• Fusion
• Injection of viral nucleic acid into the host cell

• In endocytosis, a number of mechanisms draw cells to surround and engulf the viral
particle forming a cytosolic vacuole.
• Usually occurs in but not limited to non-enveloped viruses

• In fusion, the viral envelope fuses directly with the host’s cell membrane with capsid
liberated within the cytoplasm.
• Usually occurs in enveloped viruses

• Some viral nucleic acids are injected into the host cell without either the envelope or
capsid.
• 02/25/2023
Usually occurs in bacteriophages 49
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 Uncoating of viral particle
• Following penetration is the uncoating process. This is where the nucleic acid is
released from the capsid or the coat.

• Applicable to viruses that penetrate via endocytosis and fusion

• For viruses that penetrate via endocytosis, there is acidification of the cytosolic
vacuole followed by endosome fusion.

• This causes conformational change in capsid thereby releasing the nucleic acid
• This is mediated by helper proteins that are found in the viral nucleic acid

• The nucleic acid is released in the nucleus of the cell for some viruses and for
others near the nucleus in the cytoplasm
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 Replication of the virus

• In replication, viruses generally take over the host cell and use its synthetic
machinery to make its nucleic acid over and over again
• Basically this is the stage where several genomes of the same kind are made

• Three main mechanisms take place during replication

• Transcription of viral genes into viral mRNA
• Translation of the viral genome into proteins
• Replication of the viral genome

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• Viral replication depends on the nature of the nucleic acid
• RNA viruses will use their RNA as template for the transcription into mRNA
• DNA viruses will usually need proteins and enzymes from host to make additional
DNA which can be transcribed to mRNA
• The positive sense RNA in viruses can be used directly as mRNA
• The negative sense RNA is transcribed into a positive sense RNA using an RNA -
dependent RNA polymerase carried by the virus

• To convert RNA into DNA, retroviruses must contain genes that encode the
virus-specific enzyme reverse transcriptase, which transcribes an RNA
template to DNA.

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• Reverse transcription never occurs in uninfected host cells; the needed enzyme,
reverse transcriptase, is only derived from the expression of viral genes within the
infected host cells

• The fact that HIV produces some of its own enzymes not found in the host has
allowed researchers to develop drugs that inhibit these enzymes. These drugs,
including the reverse transcriptase inhibitor AZT (azidothymidine) , inhibit HIV
replication by reducing the activity of the enzyme without affecting the host’s
metabolism.

• This approach has led to the development of a variety of drugs used to treat HIV
and has been effective at reducing the number of infectious virions (copies of
viral RNA) in the blood to non-detectable levels in many HIV-infected
individuals.
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 Maturation(This is where virions are assembled)
• When replication ends, large amounts of viral materials will be found in the host cell

• Capsid is formed from structural proteins or self assembles

• The replicated viral genome and some viral proteins become packaged within the capsid.

• Packaging of viral components can occur within the cytoplasm or in the cell nucleus.
• For example, with influenza virus, the capsomeres are transported to the cell nucleus where they
combine with the viral RNA and assemble into helical capsids.

• Though the maturation and assembly of viruses may not be well understood, the process
of chaperone proteins may be responsible for the interaction between nucleic acid and
structural proteins.

• The complete virus is then incorporated into a vesicle which migrates to the cell surface.
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 Release of virions
• Mature virions are released from the host cell after maturation.

• This can occur in a number of different ways:

• For most non–enveloped, viruses, the virus progeny accumulates within the host
cell cytoplasm and is released following cell lysis.

• Enveloped viruses are usually released by a budding process over a period of

hours.

• Ultimately the host cell will die following damage to its metabolism and
housekeeping functions during viral replication.
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 Cultivation of viruses
• To be able to identify and study effectively viruses, they need to be propagated

• In early times of virology, host cells were used and still is the case to a lesser
extent

• Introduction of cell culture has revolutionized the cultivation of viruses and this
has led to
• Better understanding of their replication properties
• More rapid diagnosis
• Easier production of vaccine

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 Cultivation cont’d
The chick embryo
• Fertile chicken eggs, 9 – 11 days old, are used as a convenient cell system to
grow a number of human pathogenic viruses

• It is a useful system due to the presence of many tissues in the egg that supports
the growth of several viruses

• Depending on the virus in question, inoculation can be made into the developing
embryo itself or into one of the various membranes and cavities such as the
chorioallantoic membrane or the allantoic cavity.

• The eggs have to be free from specific pathogens and originate from healthy
flocks
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Fertilised chicken’s egg

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• Disadvantages include cost and other infections
• If process is not done under aseptic conditions or if process takes place in an area
where other infectious are handled

• Plant viruses need to overcome the barrier presented by the cellulose cell wall
of the plant;

• In nature this is often achieved by the piercing mouthparts of an insect vector

or by entering areas of damaged tissue.

• Experimentally, viruses can be introduced into an appropriate host by rubbing

the surface of a leaf with the virus together with a mild abrasive to create a
minor wound.
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• Other animals such as primates and rodents can be also be used to cultivate
certain types of virus

• The use of animals follows strict ethical guidelines and is extremely expensive.

• Control measure that ensure that animals are free from any form of disease
must be observed

• When animals are used as hosts to culture these viruses for any purpose,
growth of the virus is indicated by signs of disease or death.

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 Bacteriophages
• Viruses that infect and replicate in bacteria only are known as bacteriophages
(phages for short).

• Phages vary in size(ranging from about 20nm to 200nm), structure and host.

• Phages are extremely specific in their host range and some will only infect a
specific bacterial strain
• It is possible that all bacterial species can be infected by a phage

• One main difference between a phage and a mammalian/animal virus is that

phages inject their genome into the host cell.
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• Phages have several importance and notable amongst them is its usefulness as a
genetic tool for propagating and studies of viruses due to their high
concentration levels.

• Phage capsid can be icosahedral in shape, filamentous or head-tail symmetry

• The head-tail symmetry is unique to phages as it cannot be found in eukaryotic

viruses

• The head which is icosahedral in shape contains the nucleic acid and the tail is
responsible for
• Recognizing the host receptor site
• Attachment to the host
• Serve as the nucleic acid injection device
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 Replication of Phages
• In the phage replication, two cycles emerge; lytic cycle and lysogenic cycle

Lytic Cycle
• Infection with a lytic phage, also called virulent phage, results in the replication of the phage
within the susceptible bacteria and the release of infectious phage progeny from the host cell
following cell lysis
• In this cycle, phage progeny cause lysis of the bacterial cell as they exit after replication

• During release phage encodes for genes for proteins that are able to poke holes in the
bacterial cell membrane and cell wall.

• Water flows into the cell through the holes, cells expand and burst open to release hundreds
of new phages which can infect other cells nearby

• In lytic cycle phages can spread quickly and widely

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 Lysogenic cycle
• There is incorporation of the phage genome into the host genome allowing the
phage genome to be copied and passed on along with the host genome.

• The viral nucleic acid which has integrated the host genome is called prophage
and the host cell that contains the viral genome lysogenic.

• In lysogenic cycle, phage genome is not copied immediately after injection into
the host.

• It recombines with a region of the bacterial chromosome and this causes its
integration into the chromosome.
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• The prophage at this stage is inactive in that it does not drive the production of new
phages using the cell synthetic machinery.

• Not all phages integrate their genome into the bacterial chromosome. Some keep
their genome in the cell as a separate piece of genome.

• Following infection with lysogenic phages, both lytic and lysogenic responses will be
observed

• On occasions, a prophage dormant in its host can be reactivated and resume a lytic
cycle.
• Can also be induced via artificial means such as exposure to chemicals or physical agents such
as UV light/radiations

• As new phages exit the host, they can carry along genes from the host chromosome
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transmit to new susceptible cells. 68
 Cultivating Phages
• Phages are grown in a culture of their bacterial host

In liquid media,
• Stock cultures of phages can be prepared by inoculating them into a broth
culture of the appropriate bacterium.

• Clearing of the culture’s turbidity indicates successful propagation of phages.

Reason???

• The culture is centrifuged to remove any remaining bacteria, leaving the phage
particles in the supernatant.
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In a solid media,

• Phages are inoculated on to a lawn of a susceptible host bacterium in a petri dish.

• Clear ‘colonies’ known as plaques which result from phage infection and lysis of
the bacterial host cells are formed.

• The release of phage progeny, subsequent infection, replicating in, and lysing of
adjacent cells ultimately form more of these plaques.

• Plaques are easily identified with the naked eye

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 Importance of Phages
• Use of phages to control bacterial infections and product contamination
• The use of phages to combat Listeria monocytogenes in ready-to-eat meat and poultry
products
• A phage - based product to combat Pseudomonas aeruginosa in ear infection
• Phage preparations are also successfully employed in combating Lactococcus garvieae, a
disease causing organism in fishes.

• Phage typing can be used in differentiating distinct strains of bacteria due to the
bacteria’s susceptibility to the phage.

• Phages can also be used in making rapid diagnostic test kit

• Example is the kit for testing for TB. This relies on the protection of TB phages from a
viricide in the presence of M. tuberculosis.
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 Prions
• They are a class of infectious agents made up of entirely misfolded proteins and
devoid of any nucleic acid.

• In the past, certain neurodegenerative diseases like bovine spongiform

encephalopathy(BSE) in cattle, scrapie in sheep and Creutzfeldt-Jakob disease (a
fatal brain disease in man) were thought to be caused virus.

• Further research proved they are caused by the highly infectious protein prion.

• Basically they can be known as infectious proteins and they cause

neurodegenerative conditions that can be very fatal.

• They can be recovered from the brains of infected individuals as rod - like
structures
02/25/2023 which are oligomers of a 30 kDa glycoprotein. 73
 How they propagate
• They are known to transmit their misfolded state by inducing normal properly folded
proteins to become misfolded.

• There is a glycoprotein (PrPc) that has same amino acid sequence as the prion protein
(PrPsc) but different structure found in the neurons of the host.

• Prion form of the protein combines with the normal form and change its
configuration to that of the prion.

• This keeps going on till lots of normal proteins become like the prion proteins and
accumulate in the brain.

• As prions accumulate, they cause neurons to form vacuoles which ultimately build
holes in the brain’s grey matter and cause the brain to look like a spongy material.
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 Things to note
• Host should express the normal form of the prion protein to be able to cause
propagation of the disease

• Prions are extremely stable and can be resistant to protein denaturation through
chemical or physical means.

• The disease has an inevitable progression to paralysis, dementia and death.

• The incubation period of disease can be very long; about 20 years and drug design
should be targeted at slowing the progression of prion formation.

• Prions can affect plants.

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 Examples of prion diseases
• Students are to find out

• Study on symptoms, host, incubation period and everything that needs

to be known about the disease

• This is examinable

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