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PHR 124 Lecture 11

Pharmaceutical Microbiology

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0% found this document useful (0 votes)
8 views40 pages

PHR 124 Lecture 11

Pharmaceutical Microbiology

Uploaded by

Sayedul Hamim
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Department of Pharmaceutical Sciences

Pharmaceutical Microbiology I (PHR 124)

Umarah Miazi

Lecture 11: Viruses


Novel Properties of Viruses
Viruses are non-cellular entities and are not considered living
organisms.
They are extremely small, ranging from 20–300 nm in size.
Viruses infect a wide range of hosts, including bacteria,
protozoa, fungi, algae, plants, and animals.
They require a host cell to reproduce, as they lack enzymes
for metabolism and machinery for protein synthesis. Viruses
remain inactive outside a host and become active only inside.
Structure of viruses:
• Nucleic acid core: Contains either DNA or RNA (never both),
which can be single- or double-stranded.
• Capsid: A protein shell that encloses the genetic material.
• Surface molecules: Allow attachment to specific host cells.
Viruses exhibit geometric shapes
Size of Viruses
General Principles of Viruses

LibreTexts
Bacteria vs virus
Characteristic Bacteria Viruses
Cellular Structure Yes (Prokaryotic cells) No (Acellular)
Intracellular Parasite No (Most are free-living) Yes (Require host cells)
Plasma Membrane Present Absent
Reproduction Binary fission Only inside host cell
Filterable No Yes
Genetic Material DNA and RNA DNA or RNA
Metabolism (ATP) Present Absent
Ribosomes Present (70S) Absent
Antibiotic Sensitivity Sensitive Not sensitive
Interferon Sensitivity Not sensitive Sensitive
General Terms
Virus: genetic element that cannot replicate independently of a
living (host) cell. Particles of nucleic acid, protein, and
sometimes lipids.

Virology: The study of viruses

Virus particle: extracellular form of a virus; allows virus to


exist outside host and facilitates transmission from one host
cell to another

Virion: the infectious virus particle; the nucleic acid genome


surrounded by a protein coat and, in some cases, other layers
of material
Types of Viruses
Helical viruses resemble long rods and their capsids are hollow
cylinders surrounding the nucleic acid. Example: Ebola virus and
Tobacco mosaic virus
Polyhedral viruses are many-sided. Usually the capsid is an
icosahedron. These viruses are typically near-spherical. Example:
Adenovirus and Poliovirus
Enveloped viruses are covered by an envelope and are roughly
spherical but highly pleomorphic* does not have a fixed or uniform
shape. example: Poxvirus, Influenza virus.
Complex viruses They often feature complex structure such as a
polyhedral head and a helical tail. example: T4 bacteriophage, E. coli.
**Pleomorphic means having many forms. A tumour may be pleomorphic.
Corona
Ebola Virus
Virus
Icosahedral
Basic structure of virus
• Nucleic Acid
• Capsid
• Envelope
Nucleic Acid
Viruses contain either DNA or RNA, never both.
The nucleic acid may be single or double-stranded, linear or
circular, or divided into several separate molecules.

Function :

Viral genome has codes with genetic information for the synthesis of
various proteins.

Helps to replicate its genetic material to produce more of its kind.


Capsid
The protein coat surrounding the nucleic acid of a virus is called the
capsid.
The capsid is composed of subunits called capsomeres. The
capsomere can be made up of one type of protein or several
different types of proteins.
Viral capsids are of two shapes: helical and icosahedral.

Function :
• It protects the viral genome from getting digested by enzymes.
• It helps the virus to inject the infectious viral genome into the
cytoplasm of the host cell.
Envelope
Envelope is the structure that surrounds the nucleocapsid of a virus.
Viruses without an envelope are called naked viruses.

The envelope projects out as spikes in some viral structures. These


spikes help in binding the virus to the host cell.

Functions :
• helps in viral genome protection, attachment and penetration to
the host cell.

• Viruses with envelopes are adapted for changes and may cause
constant infections.
Special kind of virus :Bacteriophages
• They can be enveloped and non enveloped. They have double
stranded DNA. Example: T-even phages (T2, T4, T6, etc.)

• Bacteriophages infect and replicate only in bacterial cells.

• Phages show high host specificity. They usually inhabit the


intestinal microbial flora of humans and other animals. Examples:
They infect Escherichia virus T4, Salmonella virus, Bacillus virus.

Application : Used in drug discovery, treating antibiotic-resistant


infections, and neutralizing toxins like those in anthrax and
botulism.
Structure of Bacteriophages
Head:
• The head is made up of protein coat known as a phage capsid. It
surrounds the genome or nucleic acid molecule. capsid is
composed of individual protein units known as capsomeres.
• Mainly have single or double-stranded DNA. some carry RNA.
Tail
• The tail consists of a hollow tube through which the nucleic acid
passes into the bacterial cell during infection.
• The sheath of the tail helps to contract the tail. As a result, the
nucleic acid passes through the tail and gets into the bacterial cell
during infection.
• The tail consists of a basal plate from which spike and tail fibers
originate.
• These tail fibers and spikes bind on outer membrane of the host
cell wall.
Animal Viruses
• These viruses use animal cells as their host to reproduce. They do
not infect plants or bacteria — only animals.
• The host cell must have a specific receptor on its surface for the
virus to attach.
• The host cell must provide all necessary enzymes and materials
to produce new particles.
Some viruses infect only one species (e.g., HIV infects only
humans).Others can infect many species (e.g., Rabies virus infects
various animals).
Some viruses infect only one type of tissue within a host (e.g.,
Hepatitis viruses target liver cells).Others infect multiple tissues
(e.g., Poliovirus infects intestinal and nerve cells).
Animal Viruses
Smallpox vaccine is made from virus
grown on skin of healthy calves or
sheep. Later smallpox virus is
injected into subject to provide
protection against natural smallpox
infection.
Tobacco mosaic virus which causes
tobacco mosaic disease on tobacco
leaves do no cause infections in
humans.
Viral Multiplication
Viral Multiplication
The genetic material (nucleic acid) inside a virus particle (virion)
carries only a small number of genes.
These genes mostly code for:
• Structural parts of the virus, like capsid proteins (the outer
protein shell),
• And a few enzymes that the virus needs to complete its life
cycle inside the host cell.
Since viruses are not considered truly living cells, viral
multiplication or replication requires host cell components and
metabolic machineries. Based on the types of virus Viral
replication is generally classified into two types:
 Bacteriophages: viruses that infect prokaryotic cells (bacteria).
 Animal viruses: viruses that infect eukaryotic cells (animals)
Multiplication of Bacteriophages in
bacteria
Bacteriophages infect prokaryotic cells (bacteria). There are
two distinct pathways.
1) Lytic cycle
2) Lysogenic cycle

Depending on the life cycle, phages can either by lytic


(virulent) or lysogenic (temperate). During lytic cycle , phages
kill the cells they infect. During lysogenic cycle, phages
establish a persistent infection of the cell without killing it.
Multiplication of Bacteriophages in
bacteria
1) Lytic cycle:
Step 1: Adsorption/ Attachment
Tail of the phages attach to specific receptors
proteins on the bacterial cell surface .
Step 2: Penetration
After attachment , phages have enzymes that
digest various components of the bacterial cell
wall. After that , only its nucleic acid passes from
virus head through the hollow tail and enters the
bacterial cell. the rest of the phage remains
outside the bacterium.
Multiplication of Bacteriophages in bacteria
1) Lytic cycle..cont:
Step 3: Biosynthesis/Transcription
After the phage injects its nucleic acid into the bacterial cell-
the viral nucleic acid takes over the bacteria’s DNA. The bacterial
DNA helps produce new phage nucleic acids.
The bacteria’s metabolic pathway helps to synthesizes structure of
virus such as heads and tails.
The bacteria also produces lysozyme, which will later help the virus
to lyse the bacterial cell and release the mature virus.
Step 4: Assembly and Release
After synthesis of both structure and nucleic acids of virus, the
phage components begin to assemble. Afterwards, The assembled
phage becomes mature phages.
the bacteria begin to lyse the bacterial cell wall by enzymes and are
released. New virion then infect more cells.
Multiplication of Bacteriophages in
bacteria
2) Lysogenic cycle:
1. Attachment and Penetration: Virus tail binds to specific
receptors on the cell surface and injects genetic material (DNA)
into cell.
2. Circularization: Phage DNA circularizes and enters either lytic or
lysogenic cycle.
3. Integration: Phage DNA integrates with bacterial chromosome
and replicated along with the host chromosome . This integrated
state of phage DNA is termed prophage. This process is known
as lysogeny. Prophage remains latent.
4. Excision: The lysogenic state can get terminated anytime when
it exposed to adverse conditions (e.g. chemicals, UV radiation).
Prophage virus DNA then initiates lytic cycle resulting in cell lysis
and releases of phages. Such phages are then capable of
infecting new susceptible cells
Lysogenic versus Lytic Cycles of
Bacteriophage
Multiplication of Animal Virus in
animal cell
Step 1) Attachment
(Adsorption):
• The virus binds to specific
receptor sites on the host cell
membrane.
• Attachment occurs via capsid
proteins
• A virus may bind to multiple /
specific receptors and infect more
than one host or tissue type.
Step 2) Entry and Uncoating:
Entry : The mechanism of entry of a virus or its genome depends on
the virus structure. One of the following ways it may happen;
• Fusion (Enveloped viruses only): The viral envelope fuses directly
with the host cell membrane. This releases the nucleocapsid into
the host cell.
• Endocytosis (Common for both naked and enveloped viruses): The
virus is engulfed by the host cell into vesicles called endosomes.
Inside the host, the capsid breaks down, and the genomic
material is released.
Uncoating:
• The viral capsid is completely removed, allowing the nucleic
acid to be free in the host cell for replication.
Step 3) Synthesis (Replication and Protein Production):
Viral genome replication and protein synthesis occur. proteins for
genome replication and structural proteins for capsid and envelope.
Step 4) Assembly (Maturation):
Newly synthesized viral genomes and proteins are assembled in
nucleus and cytoplasm into complete virions.
Step 1, 2, 3, 4
Step 5) Release of Progeny Virions:
• Non-enveloped viruses: Released by cell lysis by disrupting
membranes or cell walls, often killing the host cell. Example:
Poliovirus
• Enveloped viruses: Released via budding through the host cell
membrane (plasma membrane, Golgi, ER, etc.). Envelope is
derived from host membranes and contains viral glycoproteins.
Host cell may die or survive.
• Example: Human Immunodeficiency Virus
Isolation,
Cultivation, and
Identification
Isolation, Cultivation, and Identification
of Viruses (Bacteriophage)
Bacterial viruses are easily isolated and cultivated in cultures of
bacteria in broth or on agar plates.
• In liquid cultures of bacteria which is cloudy , becomes clear
after lysing of the bacteria and phage production.
• In agar-plate bacterial culture, clear zones or plaques of
phages become visible on the to the unaided eye.

Plaques are clear zones that develop on lawns of host cells.


Quantification of Viruses by Plaque Assay
Isolation and Identification of Virus,
Cultivation of Animal Virus
Embryonated chicken eggs: The chick embryo technique has been
used in the production of vaccines against smallpox, yellow fever,
influenza and other studies whenever large amounts of virus are
required.
Tissue cultures: It is a method for the replication of viruses
because it is convenient, relatively economic. Cell lines can be
obtained from mouse, hamster, chicken or monkey tissue etc.
Animals: Living animals such as mice, guinea pigs and rabbits are
used. Animal inoculation is a good diagnostic tool since they can
show disease symptoms and tissue sections can be used for
microscopic examinations.

https://www.youtube.com/watch?app=desktop&v=LcybSfvEks8
https://www.youtube.com/watch?v=Eq9JIq9HvMg
Types of Viral Infections
1) Latent infection
In a latent infection, the virus or its genome enters the host cell and
becomes dormant. No active replication occurs during this stage, and no
viral particles are produced. At any time, usually under stress or immune
suppression, the virus can reactivate, resume replication, and cause
symptoms again. Example:
• Herpes Simplex Virus (HSV): After the initial infection (cold sores), HSV
enters a latent phase in nerve ganglia and may reactivate periodically.
• Chickenpox (Zoster Virus)
2) Persistent Viral Infection
• In persistent infections, the virus continuously replicates at low levels
without killing the host cell. The infection may last months or years, with
or without symptoms. Viral particles may be continuously or
intermittently released, which can cause chronic disease or immune
system evasion. Example:
• Hepatitis B and C Viruses: These viruses can cause long-term liver
infection and inflammation, potentially leading to liver cancer.
• Human Immunodeficiency Virus (HIV): Slowly replicates and gradually
impairs the immune system.
Difficulties in Treating Viral
Diseases
• viruses require living host cells to grow, making diagnosis
and study more complex.
• Viruses use the host's own cellular machinery for
replication, so few virus-specific targets/ drugs exist that
can be attacked without harming / damaging host cells.
• Many viral infections show no symptoms during their early
(rapid growth) phase, delaying detection and treatment.
• Viruses can escape immune surveillance by mutating
surface proteins or hiding within host cells.
• Some viruses enter a latent phase, where they remain
dormant in host cells for months or years, reactivating
under certain conditions.
• Prolonged or improper use of antiviral drugs can lead to the
development of drug-resistant viral strains, complicating
treatment further.
Bacteriophages and animal viral multiplication
compared

Bacteriophages Animal Viruses


Attachment sites are plasma
Tail fibers attach to cell wall
membrane proteins and
proteins
glycoproteins.
Viral DNA injected into host cell Capsid enters by endocytosis or
fusion
No enzymatic removal of capsid Enzymatic removal of capsid
is required. proteins
Replication takes place in
Replication takes place in
nucleus DNA viruses or in
cytoplasm
cytoplasm RNA viruses
Lysogeny Latency; slow viral infections
Enveloped viruses bud out;
Host cells lysed nonenveloped viruses rupture
plasma membrane.

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