Proliferation of

Bacteriophage, Virus, Prion

Jenica & Citra

L08 Kevin
 Virus
A. Properties
• Obligate intracellular parasites
• Ultramicroscopic size (20-450nm)
• Basic structure: capsid surrounding nucleic acid core (Can be DNA or RNA)
• Use cellular enzymes and machinery for synthesizing proteins and virus replication
• Reproduction of viruses occurs by assembly of the viral components

*Obligate à must
Obligate intracellular parasites: can only survive if it’s inside the body

B. Virus as Obligate Intracellular Parasites

• It only multiplies in permissive cells of bacteria, protozoa, fungi, algae, plants, and animals
• Lack enzymes for most metabolic processes
• Lack machinery for synthesizing proteins
• Multiply by taking control of host cell’s genetic material and regulating the synthesis and
assembly of new viruses
• In laboratories: virus is grown in cell culture, embryonic eggs, lab animals.

Additional notes:
*Virus produced in the ribosome of host cell
*Virus borrows the ribosome to reproduce
*Virus can only reproduce in living cells (cannot in agar) unlike bacteria

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 Vaccine being made in eggs:

*foto diatas yg kiri coklat2 itu plaque

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 C. Structure
• Nucleic acid genome packaged in capsid (protein coat): called nucleocapsid
• Some virus has envelope: membrane made of lipids, proteins and glycoproteins
• 2 types of capsid: helical, icosahedral
o Helical
- Ribbon like structure
- Not formed by capsomeres (but by protomers) and it folds into a helix shape
because the protomeres are thicker at one
- Diameter: type of protomeres
o Icosahedral
- 5/6 capsomere
- 12 corner
- 20 triangular
- Identical to cubic symmetry.

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 D. 6 Steps in Virus Replication
A. Adsorption or Attachment
• Binding of virus to specific molecule on host cell
• Ex: HIV glycoprotein (GP120) binds with CD4 (receptor) and CXCR4 (co-receptor) and
Influenza virus hemaglutinin (HA) binds with cyalic acid
• Cellular factors that are related to tropisme or host range:
o Specific receptor
o Viral gene expression
o Enzymes necessary for virus replication
• Examples:
Receptor and co-receptor of HIV

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Hemaglutinin and neuraminidase of influenza virus

In humans, the receptors

can be found in the upper
respiratory track, which is
why flu affects breathing.

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B. Penetration
• Viral entry: genome enters host cell
• Means of viral entry
o Endocytosis
§ The entire virion is engulfed by the cell and enclosed in a vacuole or vesicle
§ The envelope and capsid will be dissolved (uncoating) -> releases genome into the
cytoplasm
§ Example: herpes virus
o Fusion
§ Viral envelope merge with cell membrane -> release genome into cytoplasm
§ Example: mumps virus

C. Replication
• Virus control cellular machinery for its replication
• Some viruses carry enzymes to start replication
o Influenza virus: RNA dependent RNA polymerase
o HIV: reverse transcriptase, integrase
o Other necessary enzymes are provided by host cell
• Viral components produced
• Virus controls the cell machinery for its replication
• DNA virus directly translates to mRNA (using enzymes from host)
• Positive strand RNA act as mRNA - directly translated protein
• Negative strand RNA – form positive strand RNA
• Protein synthesis uses cellular machinery

D. Assembly
• Viral structural proteins and genome are assembled to form nucleocapsid before being
released out of cell
• Enveloped virus: viral spikes are interested into cell membrane and taken by virus during
budding

E. Maturation
• Completion of viral formation

F. Release
• Viruses leave cell to infect other cells
• Released when cells lysis
• The envelope of the new virus is the protein membrane of the cell (the virus takes a little bit
of the cell membrane to use as its own envelope) – budding or exocytosis

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G. Virus-Host Interaction
a. Cytopathic viruses (killer)
• Ultimately kill the host cell
• Often result in local necrosis (the death of most or all of the cell)
• Can trigger apoptosis (cell death program)

b. Non-cytopathic viruses (silent killer)

• Do not immediately cause cell death
• Causes latent or persistent infections
o Productive: virus causes persistent infection with the release of only a few new viral
particles at a time (persistent infection)
o Non-Productive: viruses don’t actively make virus at a detectable level for a period of
time (latent infection)
o Ex: tumor viruses (HPV) – changes cells to tumour cells

H. Pathogenesis of Viral Disease
• Maintain a reservoir (reservoir may be human or animal)
• Enters a host
• Contact and enter susceptible cells
• Replicate within the cells
• Release from the host cells
• Virus-host interactions stimulate host immune response

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 • Be either cleared from the body of the host, establish a persistent infection, or kill the
host
• Be shed back into the environment
o Pathogens lives but does not mitigate
o Environmental factors play a role in the survival of the pathogens outside the host
§ Influenza viruses: in cold conditions may stay active for a while, while in warm
temperatures are killed faster (good to know)
§ Pathogens released by feces may still live for some time (good to know)

Bacteriophage

v
v
v
• Bacteriophage: virus associated with prokaryotes (in this case bacteria)
• Virus that infect bacteria
• Occur in more than 140 bacterial genera and many different habitats
• Consist of: DNA and proteins
• Injects the genetic material from outside the cell
• Mostly dsDNA (double stranded DNA)
• Replication:
o Lytic cycle: new viruses are produced, results in the destruction of the infected cell and its
membrane.
o Lysogenic cycle: integration of the bacteriophage nucleic acid into the host bacterium's
genome, bacteriophage still there without disrupting the cells

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There are two ways bacteria can replicate:

1. Lytic Phase (T-even phages)
a. Attachment (specific cell receptor)
b. Penetration (genetic code injected to host cell though a tube and stops host’s DNA
replication and protein synthesis)
c. Genetic material immediately replicated
d. Production and assembly of virion parts

T-even phages in Escherichia coli (e.g. T2 and T4)
• Replication: similar stages as the animal virus
• First, they attached to host using specific receptors on the bacterial surface.
• The nucleic acid is injected through a rigid tube the phage inserts through the bacterial
membrane and wall, the empty capsid remains on the cell surface.
• Entry of phage’s nucleic acid stops host cell DNA replication and protein synthesis
• The host cell produces new phage parts, and parts spontaneously assemble into
bacteriophages.

2. Lysogenic Phase (Temperate phages)
a. Attachment (specific cell receptor)
b. Penetration (genetic code injected to host cell though a tube and stops host’s DNA
replication and protein synthesis)
c. Insertion of virus’ DNA to bacteria’s genes = inactive prophage state
d. Virus DNA replicated as bacteria replicates
e. Induction (becomes active prophage state and enters lytic cycle (production of new viruses)

Additional explanation
• Attach and penetrate into the bacterial host but new phages are not replicated or released
immediately.
• The viral DNA is inserted into the bacterial chromosome --- inactive prophage state
• Viral DNA was copied during cell replication – new cells contain the phage DNA
• On occasion, in a process called induction, the prophage in a lysogenic cell will be activated
and enter the lytic cycle of replication --- produce new viruses

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Good to know: when the virus enters the bacteria, they leave their capsids outside. From what the
lecturer said, the lecturer is not sure what happens to the capsids left outside, however it is
possible that the capsids are destroyed by the environment or by proteases of the host. It’s not
relevant since the capsids are not needed anymore by the viruses.

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Prion
• The term prion is derived from proteinaceous infectious particle
• Proteins found on the plasma membrane
• Prions are proteins found on the plasma membrane
In mammals, prions are found in the highest concentration in cells of the central nervous
system.
• The function of normal prions (denoted PrPC) is unknown.
• Aberrant or mutant prions (denoted PrPSc) are thought to be the causative agents of some
neurological disorders

Additional notes from dosen:
But there are cases the protein change become mutant and can induce difference between
cellular prion is secondary structure.

In body, we have genes for prion, but only produce cellular (normal) prions, but if it becomes
mutant and cannibal then we don’t know the mechanism but this new form of prion is born and
becomes a catalyst to make the normal prion become mutant and can cause diseases.


A. Diseases caused by Prion
a. Transmissible Spongiform Encephalonathics (TSEs)
• Altering the conformation (from α-helix to β-sheet) and becomes protease-
resistant (Prp)
• Prp would convert normal protease-sensitive PrP to become abnormal Prp (PrpSc).
This will result in different disease such as:
o Scrapie à affecting the nervous system on sheep and goats, transmitted by
placental tissue.
o Bovine Spongiform Encephalophaty (BSE) à affecting the cattle, known as
“mad cow disease”
• In human:
o Creutzfeldt-Jakob Syndrome (CJS) à hereditary, usually in older ages
o Variant CJS à similar to CJS, but occurs in younger people
o Kuru: in Papua, related to cannibalism
o Fatal familial insomnia, etc.
• Clinical symptoms: can cause brain cell death
• If you know how viral enzymes and proteins work then we can know how the anti
works

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 B. Prion Replication: Protein only Hypothesis
a. Template directed refolding hypothesis

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 b. Seeded nucleation hypothesis

For better understanding of replication process

• https://www.youtube.com/watch?v=uFXuxGuT7H8
• https://www.youtube.com/watch?v=3DP-MAhr0YY
• https://www.youtube.com/watch?v=HhhRQ4t95OI
• https://www.youtube.com/watch?v=YSgkoldBNkI
• https://www.youtube.com/watch?v=AZOnAuElJHk
• https://www.youtube.com/watch?v=Xws0_I-xyOI
• https://www.youtube.com/watch?v=wLoslN6d3Ec

links are from the ppt.

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