Virology

Lecture 3: Introduction to virology By Dr. Maha Adel

Definitions:

Virology: the science which deals with study of viruses as

causative agents of very important diseases that occurs in human,
animals, plants and other living organisms (insects, bacteria,…).

Viruses: They are the smallest and simplest form of life on earth,
which can replicate only in living susceptible cells. Viruses consist
of:

1- A nucleic acid genome either DNA or RNA.

2- A protein coat (capsid) that enclosed the genome.
3- In some cases a lipid membrane (envelope).

Virion:A complete infectious virus particle.

Capsid = protein shell which surrounds and protects the genome.

It is built up of multiple (identical) protein sub-units called
capsomers. Capsids are either icosahedral or tubular in shape.

Nucleocapsid = genome plus capsid

Envelope = lipid membrane which surrounds some viruses. It is

derived from the plasma membrane of the host cell.

Peplomers = proteins found in the envelope of the virion. They

are usually glycosylated and are thus more commonly known as
glycoproteins.

What is a virus?
Viruses are uniquely different from the many uni-cellular micro-
organisms you have studied so far. protozoa, yeasts, bacteria,
mycoplasmas, rikettsiae and chlamydiae are all living organisms
with the following features in common:

1. They are all cells

2. They store their genetic information as DNA

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3. Within their cell, they contain all the organelles necessary for
producing energy and synthesizing proteins,
carbohydrates, cell wall structures etc.
4. Replicate by means of binary fission

Viruses do not share these properties. They are not cells.

They are very simple structures consisting essentially of a nucleic
acid genome, protected by a shell of protein. They are
metabolically inert and can only replicate once they are inside a
host cell.

The genome consists of only one type of nucleic acid: either RNA
or DNA. Most DNA viruses are double stranded and most RNA
viruses have a single stranded (ss) genome. A ssRNA genome may
be either positive sense (this means that it can be used as mRNA to
make proteins) or negative sense. Negative sense RNA is
complimentary to mRNA, in other words, it has to be copied into
mRNA. The viral genome codes only for the few proteins necessary
for replication: some proteins are non-structural e.g. polymerase
and some are structural, i.e. they form part of the virion
structure.

They have no organelles.

They are very small, sizes range from 20 to 500 nm. This is
beyond the resolving power of the light microscope.

General characters of viruses:

1. Virus particles are very small in size; they are between 20-500
nm (nanometer) in diameter.( 1 nm= 1/1000 μm, 1 μm=1/1000
mm).
2. Viruses are obligatory intracellular microorganisms.

3. Multiply inside the cells by replicating their genomes which either

DNA or RNA, but not both.

4. The virus dose not contain any organelles (ribosomes, t RNA,

metabolic enzymes, etc), but they depend on infected cells to
provide all their needed organelles.

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5. Virus does not affect with antibiotics.

6. Most viruses sensitive to interferon.
7. Viruses can not grow on artificial media, but only in living cells
(specific host,Lab. Animals, chicken embryonated eggs & tissue
culture).
8. Some viruses cause latent infection.
9. Viruses can not be seen by ordinary microscope, but only by
Electron microscope(EM).

According to size, we can classify beginning from the largest and

more complex Microorganisms as following protozoa, yeast,
bacteria, mycoplasma, rickettsiae, chlamydia & virus.

Structure of viral nucleic acids:

Genetic information are stored as the following:
1. Double stranded DNA cells (animal, plants, bacteria and some
viruses).
2. Single-stranded DNA in other viruses (phage ϴ x 174).
3. Single stranded RNA (myxovirus).
4. Double-stranded RNA (reoviruses).

How we can differentiate between DNA and RNA? By DNAase

or RNAase.
Between double and single stranded NA? by acridine orange
stain, which is yellowish- green in double stranded and red orange
in single stranded.

Viral proteins:
Protein coat which encloses the viral genome called capsid which
consists of protomers that accumulated to give pentan or hexan
forms producing the capsomers which protect the viral NA and
have surface characters acts to attach the virus on host
cells then penetration, also it contains antigenic determinants.

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Viral envelope:
Most viruses contain envelope or membrane surrounding the virus
so they called enveloped viruses, others have no envelope and
they called naked viruses. Enveloped viruses contain lipids like
orthomyxo and paramyxo viruses, these viruses will
become sensitive to organic solvents (ether, alcohol, chloroform),
these characters used in newly isolated virus classification.
Also viral membrane contains glycolipids or glycoprotein which
appears as projections from the envelope called spikes or
peplomers.

Viral shape structure

Nucleocapsid is the arrangement between the viral nucleic acid

genome with the capsid, this connection controlled by specific NA
genetic information leading to different types of symmetry.
Accordingly viruses can classified in to four symmetry
structures.

1. Helical symmetry.
2. Cubical symmetry.
3. Binal symmetry.
4. Complex symmetry.

1. Helical symmetry
This form can be seen in RNA viruses, that the capsomers
surrounded the N.A in spiral or helical manner to give helical
symmetry which may be seen in naked or enveloped viruses.

2. Cubical symmetry
The virus particles have hexagonal outlines with 20 equilateral
triangular faces, i.e. icosahedrons.
e.g. for cubical symmetry viruses: adeno and picorna which are
naked,herpes and toga which are enveloped.

3. Binal symmetry
This type of symmetry show both icosahedral (cubical) and helical
symmetry, but within the same virion like bacteriophage, when the
head is cubical and the tail is helical.

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4. Complex symmetry
Most animal viruses show either helical or cubical symmetry but
pox viruses have exceptional and their ultra structure appears to be
complex.
Classification of Animal Viruses

Animal viruses can be classified into several families according to

the following characters:

A- Characters of viral nucleic acid (N.A).

B- Characters of viral capsid.

According to all above characters recently animal viruses classified

into two major Groups which are RNA group & DNA group as
following:

RNA Viruses families:

1. Picornaviridae
2. Orthomyxoviridae
3. Paramyxoviridae
4. Coronaviridae
5. Reoviridae
6. Retroviridae
7. Rhabdoviridae
8. Birnaviridae
9. Bornaviridae
10. Bunyaviridae
11. Togaviridae
12. Astroviridae
13. Arteriviridae
14. Caliciviridae
15. Flaviviridae

DNA Viruses families:

1. Herpesviridae
2. Poxviridae

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3. Adenoviridae
4. Parvoviridae
5. Papillomaviridae
6. Asfaviridae
7. Circoviridae

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Viral replication

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Lecture 3: Introduction to virology By Dr. Maha Adel

Replication of viruses

Viruses are the ultimate parasite. They are totally dependent on a

host cell to replicate (make more copies of itself). While the
sequence of events varies somewhat from virus to virus, the
general strategy of replication is similar:

Adsorption: The surface of the virion contains structures that

interact with molecules (receptors) on the surface of the host cell.
This is usually a passive reaction (not requiring energy), but highly
specific. It is the specificity of the reaction between viral protein
and host receptor that defines and limits the host species and type
of cell that can be infected by a particular virus. Damage to the
binding sites on the virion or blocking by specific antibodies
(neutralization) can render virions non-infectious.

Uptake: The process whereby the virion enters the cell. It occurs
either as a result of fusion of the viral envelope with the plasma
membrane of the cell or else by means of endocytosis.

Uncoating: Once inside the cell, the protein coat of the virion
dissociates and the viral genome is released into the cytoplasm.

Early phase
Once the genome is exposed, transcription of viral mRNA and
translation of a number of non-structural ("early") proteins takes
place. The function of these is to replicate the viral genome.

Genome replication
Multiple copies of the viral genome are synthesized by a viral
polymerase (one of the "early" proteins).

Late phase
Transcription and translation of viral mRNA and synthesis of the
structural ("late") proteins which are needed to make new
virions.

Assembly of new virions

Assembly of new viral capsids takes place either in the nucleus
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(e.g. herpesviruses) or in the cytoplasm (e.g. poliovirus) of the cell,

or sometimes, just beneath the cell surface (e.g. budding viruses
such as influenza). The proteins self assemble and a genome enters
each new capsid.

Release of progeny virions

Release of new infectious virions is the final stage of replication.
This may occur either by budding from plasma membrane or else
by disintegration (lysis) of the infected cell. Some viruses use the
secretory pathway to exit the cell: virus particles enclosed in golgi-
derived vesicles are released to the outside of the cell when a
transport vesicle fuses with the cell membrane.

How do viruses cause disease?

Viruses contribute significantly to the global burden of infectious

disease.
We experience countless infections throughout their lives, with
particularly high frequency in early childhood. While most of these are
mild, viruses may cause severe disease in susceptible individuals,
such as the mal-nourished, immuno-compromised, the very old and
the very young. Recent years have also seen the emergence of new
viral diseases such as HIV, SARS and "swine flu" (H1N1 pandemic
influenza A).

Viruses are capable of infecting all types of living organism from

bacteria to humans, (including plants and insects!). A major factor
that controls which cell type a virus can infect (cell tropism) is the
presence (on the cell surface) of the appropriate receptor, to which
the virus must attach in order to gain entry into the cell.

Viruses enter the body by inhalation, ingestion, sexual

intercourse or inoculation through the skin or mucous membranes.
Infection may also sometimes be passed from a mother to her foetus
transplacentally (vertical transmission). Once a virus has gained
entry into the body, infection may either remain localised to the site
of entry (an example of this is influenza where the virus remains
confined to the respiratory tract), or it may cause a disseminated
infection. Here, the virus replicates initially at the site of entry, but
then enters the blood (viraemia) or lymphatics and spreads

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throughout the body (e.g. Measles). Other viruses such as Rabies and
Herpes Simplex may replicate locally initially, then enter nerve
endings and travel up the axon to infect the central nervous
system.

The term incubation period defines the time from exposure to an

organism to the onset of clinical disease. In general, viruses that
cause localized infections have short incubation periods (<7 days),
while in disseminated infections, the incubation period tends to
be longer.

Both viral and host factors contribute to clinical disease during the
course of a viral infection. Host immune cells release interferons and
other cytokines which induce the symptoms of fever and malaise.
Tissue specific damage may be due to virus-induced lysis of
infected cells or due to inflammation and destruction of infected cells
by the host's immune response. Because viruses
replicate intracellularly, recovery from a viral infection requires the
action of specific cytotoxic T- lymphocytes which recognise and
eliminate virus-infected cells. Virus-specific antibody levels rise during
the course of the infection, but antibody plays only a limited role in
recovery from an established infection for most viruses. Nonetheless
specific antibody plays a very important role in preventing re-
infection of the host with the same virus.

An effective immune response can eliminate most viruses from the

body and thus most viral infections are short lived. However, there
are certain viruses that are able to evade the immune response and
establish persistent infections in their host. The most famous
example of such a virus is HIV, but there are many others. Viruses
use a variety of strategies to evade the immune system. On the
whole, these persistent infections are asymptomatic and only manifest
clinically if the patient becomes immuno-compromised.

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