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VIRUSES, Viroids and

Prions
Viruses
DEFINITION
- intracellular parasites
HISTORY
16th century:
• major impact on public health ie.small pox , responisble for death of millions
of Aztecs eg. Small pox

1700’s
• Edward Jenner noted that exposure to certain animal virus, such as cowpox,
extended immunity to the human small pox virus

1800’s
Louis Pasteur
• In vivo studies, inoculating the brains of dogs and spinal cords of rabbits to
isolate pure cultures of the virus
• Lead to the development of rabies vaccine

1900’s
Ivanovski and Beijerinck
- discovery of Tobacco mosaic virus (mottling of the tobacco leaf)
• Over the next 50years discovery of yellow fever, rabies, polio, measles,
mumps, rubella and more
• 1939- electron microscope developed which increase studies in Virology
General Characteristics
Definition: they are obligatory intracellular parasites.

- They contain a single pair of nucleic acid, either DNA or


RNA

- They contain a protein coat that surrounds the nucleic


acid

- They multiply inside living cells using the machinery of


the cell.

- They can transfer the viral nucleic acid to other cells.


HOST RANGE
- The host range of a virus is the spectrum of host cells the virus can
infect.

- Most viruses are able to infect specific types of cells of only one
host species

- Viruses that infect bacteria are called bacteriophage.

What determines the particular host range of a virus?


1. The virus´s requirements for its specific attachment to the host cells

2. The availability within the potential host of cellular factors required


for viral multiplication.
What must occur for the virus to infect a cell?
- The outer surface of the virus must chemically interact with specific
receptor sites on the surface of the cell.

- The two complementary components are held together by hydrogen


bonds. Ie. For bacteriophages the receptor is part of the cell wall of
the host. In other cases it’s the fimbrae or the flagella
Viruses

Figure 13.1
General Morphology
1. Helical- resemble long rods that may be rigid or flexible.
The nucleic acid is found within a hollow cylindical
capsid. (Ebola hemorrhagic fever, rabies)
2. Polyhedral Viruses- capsid is in the shape of a
meicosahedron. The capsomeres of each face form
and equilateral traingle. (polio virus)
- Enveloped polyhedral (herpes simplex virus)
3. Enveloped virus- roughly spherical (influenza)
4. Complex viruses- bacteriophages. Have capsid to
which additional structure are attached.
Viral structure
Helical Viruses

Figure 13.4a, b
Polyhedral Viruses

Figure 13.2a, b
Complex Viruses

Figure 13.5a
Typical Viral Structure
Structure
1. outer protein capsid structure
– composed of a number of protein capsomers
– Simple virion capsids are constructed from 3
proteins, whereas complex viral coats are
composed of several hundred.
– Contain numerous receptor sites and electrical
charges.

• Function:
– protects and shield the viral nucleic acid and
harbors specific receptor sites for host attachment.
– Aids in virus concentration
Note: In some viruses the capsid is covered by a
envelope
2. outer membrane layer or envelope

- this outer membrane is form by budding from host membrane cells


and thus, they retain part of the host cell outer structure.
- It is made up of lipid bi layers
- it contain glycoprotein to add rigidity for fusion with the host and
subsequent infection
- May have spikes that project from the surface. These may bind
to RBC´s and form bridges between them. The resulting
clumping is called hemagglutination
• Viruses whose capsid is not covered by an envelope are known
as nonenveloped viruses.
- the capsid of a noneneveloped virus protects the nucleic fluids and
promotes the virus´s attachment to susceptible host.
3. contains either DNA or RNA in the double
stranded or single stranded form
• - length of nucleic acid corresponds directly to
virus
- Most virus contains less than 10 genes
– All virus requires messenger RNA (mRNA) which is
translated to proteins to allow viral replication
– RNA viral genomes tend to be much smaller and code
for fewer proteins than DNA genomes.
• Function:
– to transcribe the original nucleic acid into a readable
mRNA sequence (transcription) for the production of
protein. (translation)
What happens when a virus infects a host?
- The host immune system is stimulated to produce antibodies. This
interaction between antibodies and the virus proteins should
inactivate the virus and stop the infection.

So, Why does infection sometime persist?


- The viruses escape antibodies because regions of the gene that
codes for these viruses surface proteins are susceptible to mutation.
Ie. Influenza
Role of Bacteriophage
Phage population correlates with fluctuations in the
microbial community brought on by spring diatom bloom.

1. Lysing bacterial cells that may otherwise might be


available for predator by heterotrophic flagellates.

2. involved in the parasitism of bacterial populations

3. affect a variety of primary producers such as diatoms,


cryptophytes and cyanobacteria.

* Population is controlled by aggregation and adsorption to


non host particles creating a phage biomass that is
available to detritus feeders.
What mechanisms associated with viruses aid
in the persistence and survivability in the
environment?
1. the adsorption (sticking) of viruses to
sediments.
2. sediment dwelling organisms serving as viral
host
3. the phage involvement in transduction.
Note:
Transduction is a process by which they multiply in
a donor bacterium and carry a piece of genetic
material to a recipient bacterium that they
subsequently infect.
Culturing Bacteriophages
- Grown in suspensions of bacteria in liquid media or bacteria cultures on
solid media.
Plaque method
- A sample of bacteriophage is mixed with host bacteria and melted agar.
- The agar containing the bacteriophage and the host bacteria is then
poured in a petri dish containing a harden layer of agar growth medium.
- The virus bacteria mixture solidifies into a thin top layer that contains a
layer of bacteria approximately 1 cell thick
- Each virus infects a bacterium, multiplies, and releases several hundred
new viruses.
- The newly produced viruses affect other bacteria in the vicinity and
more new viruses are produced.
- Eventually all the bacteria are destroyed and it produces a number of
clearing or plaques.
- Each plaque corresponds to a single virus
Growing Animal Viruses in the Laboratory
1. In living animals
- Cultured in living animals such as mice, rabbits and guinea pigs
- Animals are inoculated and observed for signs of disease or is
killed so that infected tissue can be examined for the virus.

Note: AIDS vaccines are presently being tested in humans, but the
disease progresses so slowly in humans that it can take years to
determine the effectiveness of these vaccines.

- In 1986, simian AIDS (an immunodefficiency disease of green


monkeys) was reported and in 1987 feline AIDS in cats. Both are
cause by lentiviruses closely related to HIV and can thus be used
as a model for studying the viral growth in different tissues.

- In 1990, a way to infect mice with human AIDS was found .


2. In Embryonated eggs
- A hole is drilled in the shell of the embryonated egg, and
a viral suspension is injected into the fluid of the egg.
- Viral growth is signaled by the death of the embryo cell
damage, or by the formation of typical pocks or lesions
on the egg membrane.
Growing Viruses

• Animal
viruses may
be grown in
living animals
or in
embryonated
eggs.

Figure 13.7
3. In cell cultures
- Consist of cells grown in culture media in the lab.
- Cell culture lines are started by treating a slice of animal
tissue with enzymes that separate the individual cells.
- These cells are suspended in a solution that provides
the osmotic pressure, nutrients, and growth factors
needed for the cells to grow.
- Normal cells tend to adhere to the glass or plastic
container and reproduce to form a monolayer.
- Viruses affecting the monolayer sometimes causes the
cells to deteriorate as they multiply. (cytopathic effect)
Growing Viruses
• Animal and plants viruses may be grown in cell culture.
– Continuous cell lines may be maintained indefinitely.

Figure 13.8
Infective Nature of Viruses
A. Mechanism of transmission
– aerosols (measles, mumps, influenza)
– vectors ( yellow fever, dengue)
– contamination of food
– person to person (exposure, blood, urine, sex, placenta)
– cross specie (rabies, ebola)

How do they affect their host?


1. contact potential host
2. they find their way into the target cell using specific
receptors sites on their caspsid or envelope surfaces.
3. Once they invade that host cell and replicate, they can
invade neighboring cells to continue the infection
process.
Types of viral infections
1. asymptomatic- virus replicate effectively without killing
the host and may cause no symptoms. Eg. Herpes
2. Acute- has an episode of illness directly associated
with infection. Ie. Common cold
3. Chronic (persistent)- no immediate sign of infection, but
host are still able to shed virus eg, hepatitis B and C
4. Latent-may be present and even integrated in the host
chromosomes but do not produce progeny virions
unless presented with an appropriate stimulus. Eg.
Common cold virus, fever blisters, genital herpes,
chicken pox, shingles
5. Slow infections- gradually increases in effect and
progress to a lethal conclusion. Ie. HIV, lentivirus
6. Cause death eg. Polio (cause death of cell), HPV
(cancer)
Types of Virus
1. Latent Viruses: is the ability of a pathogenic virus to lie
dormant within a cell, denoted as the lysogenic part of
the viral life cycle. Examples: HSV-1 and HSV-2;
varicella

2. Oncogenic Virus
– do not kill their host but do alter its functioning,
directing the production of cancer cells.
– oncovirus is a virus that can cause cancer.
• Examples of human tumors:
– Kaposi’s sarcoma (herpes virus)
– Squamous cell carcinomas (HPV)
– Hepatocellular carcinoma (HBV and HCV)
Oncogenic Viruses

• Oncogenic DNA
 Oncogenic RNA
Viruses viruses
– Adenoviridae
 Retroviridae
 Viral RNA is
– Heresviridae transcribed to DNA
– Poxviridae which can integrate
into host DNA
– Papovaviridae
– Hepadnaviridae
3. Cytopathogenic virus

– virus that kill the cells in which they replicate


– shuts down the synthesis of cellular proteins, using
structures assembled late in the virus replication
cycle that are toxic to host.

4. Lysogeny- condition where viral infection of bacteria


appear to cause no immediate harm to most cells.
The host carries the phage and therefore may be
sensitive to other phage population.

5. Prophage- a stable, non infectious form of virus in


the lysogenic phage/ temperate phage where the
nucleic acid is integrated with the chromosome of
the host, persisting indefinitely and is transmitted to
host descendants on daughter cells.
The metabolic state of Viruses
Viruses have 2 stages in their life cycle:
a. ECLIPSE
-phase during which the virion has entered the cell
and before progeny virus are made.
-No infectious virus are present during this phase
- period in which virus gains control of host synthetic
machinery and produce components required to
assemble into virus

b. LATENT PHASE
-The period following the eclipse phase from time of
disappearance of the infecting virus to the appearance
of infectious virus in the surroundings
- Virus are internal and must be released to be
assayed
The Lytic Cycle
• The lytic cycle is one of the two cycles of viral reproduction, the
other being the lysogenic cycle.

• The lytic cycle is typically considered the main method of viral


replication, since it results in the destruction of the infected cell.

• A key difference between the lytic and lysogenic phage cycles is


that in the lytic phage, the viral DNA exists as a separate molecule
within the bacterial cell, and replicates separately from the host
bacterial DNA.

• The location of viral DNA in the lysogenic phage cycle is within the
host DNA, therefore in both cases the virus/phage replicates using
the host DNA machinery, but in the lytic phage cycle, the phage is a
free floating separate molecule to the host DNA.
T-EVEN BACTERIOPHAGES : The Lytic cycle
1. Attachment (absorption)- based on specific recognition
– binding between viral capsid protein and specific receptors on
the host cellular surface. ( Species barrier) ie human polio virus
(isolated in brain, nerve or intestinal cells)
– ENVELOPED VIRUS utilizes glycoprotein spikes for specific
host attachment and many bacteriophage utilize tail structures to
inject nucleic acid into the host.
– This attachment is a chemical interaction in which weak bonds
are formed between the attachment and the receptor sites.

2. Penetration
- The T-even bacteriophage injects its DNA into the bacterium by
releasing an enzyme phage lysozyme that breaks down a
portion of the bacteria cell wall.
- When the tip of the core reaches the plasma membrane, the
DNA from the bacteriophage head passes through the tail core,
through the membrane and enters the bacterial cell.
- The capsule remains outside the bacterial cell.
3. Biosynthesis:
- Once the bacteriophage DNA has reached the
cytoplasm of the host cell, the biosynthesis of viral
nucleic acid and protein occurs.
- Initially, the phage uses the host cells nucleotides and
several of its enzymes to synthesize many copies of
phage DNA.
- Soon after the biosynthesis of viral proteins begins
- Transcription of phage DNA produces mRNA coding for
proteins necessary for phage multiplication.
- Phage DNA is replicated, and capsid protein are
produces.
- During the eclipse period, separate phage DNA and
protein can be found.
4. Maturation
- In this process, bacteriophage DNA and capsids are assemble into
complex virions.
- The phage heads and tail are separately assembled from protein
subunits, and the head is filled with DNA and attached to the tail.

5. Release
- Phage lysozyme breaks down the bacteria cell wall and the new
phages are release.
The lytic cycle of phage T4
The Lysogenic Cycle
- In contrast to T-even bacteriophage some viruses do not cause lysis
and death of the host cell when they multiply.
- In lysogeny the phage remains latent (inactive)
1. Phage attaches to host cell and injects its DNA.
2. The original linear phage DNA forms a circle
3. (A)This circle can multiply and be transcribed (assembled into virions)
Or (b) the phage DNA integrates within the bacterial chromosomes by
recombination and becomes a prophage.
4. If (A) occurs, cells lyses releasing virions
- If (b) occurs, the lysogenic bacteria reproduces normally (many cell
divisions). The phage remains dormant within the progeny cells.
5. Occasionally, spontaneously or due to action of UV light the
prophage may excise (pop out) from the bacterial chromosome
initiating a lytic cycle.
The lysogenic and lytic reproductive cycles of phage , a temperate phage
Multiplication of Animal viruses

• Attachment Viruses attaches to cell


membrane
• Penetration By endocytosis or fusion
• Uncoating By viral or host enzymes
• Biosynthesis Production of nucleic acid and
proteins
• Maturation Nucleic acid and capsid proteins
assemble
• Release By budding (enveloped viruses) or
rupture
Attachment, Penetration, and Uncoating
Entry and Uncoating of Animal Viruses

Figure 13.12a-b
Transcription Strategy
Multiplication of DNA Virus
Papovavirus 1 Virion attaches to host cell
7 Virions are released
Host cell
DNA
Capsid

DNA 2 Virion penetrates


cell and its DNA is
6 Virions mature Cytoplasm
uncoated

Capsid proteins

mRNA

5 Late translation;
capsid proteins
are synthesized

3 Early transcription and


4 Late transcription; translation; enzymes are
DNA is replicated synthesized
Multiplication for RNA-Containing
Viruses
Prions
• Infectious proteins that are Inherited and also transmissible
by ingestion, transplant, & surgical instruments
• No nucleic acid involved
• Cause degenerative brain diseases
– Spongiform encephalopathies: Sheep scrapie, Creutzfeldt-
Jakob disease, Gerstmann-Sträussler-Scheinker syndrome,
fatal familial insomnia, mad cow disease, Kuru
– Prion diseases are often called spongiform
encephalopathies because of the post mortem appearance
of the brain with large vacuoles in the cortex and
cerebellum
Viroids
• Short pieces of
“naked” RNA
• No Protein coat
• Only known to
infect plants
• Cadang Cadang
disease
Viruses and Cancer
- When activated, oncogenes transform normal cells into cancerous
cells.

- Viruses capable of producing tumors are called oncogenic viruses

- Several DNA viruses and retroviruses are oncogenic.

- The genetic material of oncogenic viruses become integrated into


the host cell´s DNA

- Transformed cells loose contact inhibition, contain virus specific


agent (TSTA and T antigen), exhibiit chromosomes abnormalities,
and produce tumors when injected into susceptible animals.
Cancer

• Activated oncogenes transform normal cells


into cancerous cells.
• Transformed cells have increased growth,
loss of contact inhibition, tumor specific
transplant and T antigens.
• The genetic material of oncogenic viruses
becomes integrated into the host cell's DNA.
HIV, a retrovirus
Mumps, Measles, Influenza, and
Poliomyelitis
Chickenpox
- Varicella
Blister-like rash on surface
of skin and mucous
membranes. Blisters
usually appear first on
trunk and face, then
spread to almost
everywhere else.
Shingles or
Herpes Zoster
About 20 % of those people who
have had chicken pox will get
zoster at some time during their
lives. Most people will get zoster
only once.
Double-stranded DNA, non-enveloped viruses

 Mastadenovirus
 Respiratory
infections in
humans
 Tumors in
animals
Double-stranded DNA, non-enveloped viruses

 Mastadenovirus
 Respiratory
infections in
humans
 Tumors in
animals
Double-stranded DNA, non-enveloped viruses
 Orthopoxvirus
(vaccinia and
smallpox
viruses)
 Molluscipoxvirus
 Smallpox,
molluscum
contagiosum,
cowpox
Double-stranded DNA, non-enveloped viruses

 Hepadnavirus
(Hepatitis B
virus)
 Use reverse
transcriptase to
produce DNA
from mRNA
Single-stranded RNA, + strand, non-enveloped

 Enterovirus
 Enteroviruses
include
poliovirus and
coxsackievirus
 Hepatitis A
virus
Single-stranded RNA, + strand, non-enveloped

 Hepatitis E virus
 Norovirus
(Norwalk agent)
causes
gastroenteritis
Single-stranded RNA, + strand, non-
enveloped

 Rubivirus
(rubella virus)
Single-stranded RNA, + strand, non-enveloped

 Arboviruses can
replicate in
arthropods; include
yellow fever, dengue,
and West Nile
viruses
 Hepatitis C virus
Single-stranded RNA, + strand, non-enveloped

 Coronavirus
 Upper
respiratory
infections
Single-stranded RNA, – strand, one RNA
strand

 Vesiculovirus
 Lyssavirus
(rabies virus)
 Cause numerous
animal diseases
Single-stranded RNA, – strand, one RNA
strand

 Filovirus
 Enveloped,
helical viruses
 Ebola viruses
Single-stranded RNA, – strand, one RNA
strand

 Hepatitis D
virus
Single-stranded RNA, – strand, multiple RNA strands

 Influenzavirus
(Influenza
viruses A and B)
 Influenza C
virus
 Envelope spikes
can agglutinate
RBCs
Single-stranded RNA, two RNA strands,
produce DNA
 Lentivirus (HIV)
 Oncogenic viruses
 Use reverse
transcriptase
to produce
DNA from viral
genome
 Includes all
RNA tumor
viruses

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