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VIROLOGY
Study of viruses
MR E.E
Aims and Objectives
• At the end of this course, you should be able to:
– Discuss what constitutes a living organism.
– Define what constitutes a virus.
– Have a knowledge of the principle viral structures,
classification and replication of major viruses of medical
importance.
– Have a knowledge of how viruses cause diseases
– Understand the principles of diagnosis of virus infections.
– Know the mechanisms of action of antiviral drugs used in
clinical practice.
Definition of a Virus
• Virus is the Latin name meaning slime or poison
• A virus is the smallest infectious agent with a molecule of NA
for its genome that can only be propagated in the presence of
living cells.
• Viruses are organized associations of macromolecules, nucleic
acid contained within a protective shell of protein units.
• On its own, a virus may be considered as an inert
biochemical complex since it cannot replicate outside of a
living cell.
• Once it has invaded a cell it is able to direct the host cell
machinery to synthesize new intact infectious virus particles
(virions).
• Since viruses are non-motile, they are entirely dependent on
external physical factors for chance movement and spread to
infect other susceptible cells.
Definitive Properties of Viruses
• A virus is a small, infectious, obligate intracellular
parasite, capable of replicating itself in a host cell.
• The defining properties of viruses are as follows:
– Viruses are obligate intracellular molecular parasites,
which are very small and infectious.
– The virus genome is composed either of DNA or RNA.
– The virus genome directs the synthesis of virion
components within an appropriate host cell.
– Progeny virus particles are produced by the assembly of
newly made viral components.
– Progeny virus particles spread infection to new cells.
Historical Perspective
• Many viruses have co-evolved with mammals and other
animals over long periods of time.
– Examples of such viruses are Herpesviruses, which have
been traced back to fish and birds, as well as mammals. It
is thought that herpesviruses have existed for two hundred
million years or longer, and that they have infected humans
since the early times of our speciation.
• Other viruses have entered human populations only recently,
– due to changes in agriculture (use of domestic animals),
– population dynamics (urbanization),
– migration of populations, commerce and changes in the
environment.
– Examples of these agents include the SARS, coronavirus,
measles virus and HIV-1.
Discovery of viruses
• In the 1890s, the agent that caused tobacco mosaic disease was
a filterable agent smaller than bacteria was discovered.
• By the early 1900s, additional viruses including viruses that
caused tumors in chickens (e.g., the Rous sarcoma virus) as
well as yellow fever virus (the first human virus to be
discovered, in 1901).
• The first virus was purified in 1933 by Schlessinger using
differential centrifugation.
• In 1935, Stanley isolated the tobacco mosaic virus in
paracrystalline form.
• In 1937 Bawden and Pirie extensively purified tobacco mosaic
virus and showed it to be a nucleoprotein containing RNA.
• In 1957, Fraenkel-Conrat and Singer confirmed the hereditary
role of viral RNA by dissociating the particles of tobacco
mosaic virus into protein and RNA components
VIRUS STRUCTURE
• Viruses are very small in size (20 - 300 nanometers) and
contain either DNA or RNA (not both as in higher forms of
life).
• The genome, (DNA or RNA) codes for the few proteins
necessary for replication.
• Some proteins are non-structural, e.g. nucleic acid,
polymerases
• Some are structural, i.e. they become incorporated and form
part of the virion.
• Protein building blocks are assembled to form a tight "shell"
(capsid) inside which the nucleic acid genome lodges for
protection.
• All the viral proteins have reactive epitopes, which are
important for interaction with cellular components during the
process of infection and replication. The host's defence
mechanism
• The CAPSID denotes the protein shell that encloses the
nucleic acid. It is built of structure units.
• STRUCTURE UNITS are the smallest functional equivalent
building units of the capsid.
• CAPSOMERS are morphological units seen on the surface of
particles and represent clusters of structure units.
• The capsid together with its enclosed nucleic acid is called the
NUCLEOCAPSID.
• The nucleocapsid may be invested in an ENVELOPE, which
may contain material of host cell as well as viral origin.
• The capsid shell may take the form of a polyhedron (usually
icosahedral) or it may be spiral (helical symmetry), or it may
be more complex.
• Some viruses acquire an outer lipoprotein coat by
"budding" through the host cell membranes (nuclear
membrane or cytoplasmic membrane) and are thus
called enveloped viruses.
• Majority of the viruses (with the exception of a few
bacteriophages) fall into two main morphological
groups: Those with cubic symmetry and the others
with helical symmetry.
• The terms "capsid" and "capsomers" represent,
respectively, the protein shell and the units
comprising it, and the term "virion" denote the
complete infective virus particle (i.e. a capsid
enclosing the nucleic acid).
Shape
• Simply
– Spherical: most viruses that cause animal diseases
– Rod shaped: some plant viruses
– Tadpole bacterial viruses
• Geometrically
– Icosahedral: many-sided geometric form with triangular
faces and apexes, have cubic symmetry
– Helical: spiral tubular structure bound up to make a
compact long rod
– Complex: enclosed by a loose covering envelope which is
not rigid, thus giving variable size and shape
Icosahedron/Cubic Symmetry
• An icosahedron is composed of 20 facets,
each an equilateral triangle, and 12 vertices,
and because of the axes of rotational symmetry
is said to have 5:3:2 symmetry.
• Axes of Symmetry
– six 5-fold axes of symmetry passing through
the vertices,
– ten 3-fold axes extending through each face
and
– fifteen 2-fold axes passing through the edges
of an icosahedron
Icosahedron/Cubic Symmetry
Helical Symmetry
• "Linear" viral capsids have genomes that are
encased in a helix of identical protein subunits.
• The length of the helical viral nucleocapsid is
determined by the length of the nucleic acid
• Until 1960, the only known examples of
virions with helical symmetry were those of
plant viruses
• Some affecting mammals like the Rabies virus
also occur
HELICAL SYMMETRY
SIZE
• SMALL AND SIMPLE
– 20 NM IN DIAMETER, CONTAIN A DOZEN
OF GENES
• LARGE AND COMPLEX
– 200 – 300 NM IN DIAMETER,
– SEVERAL HUNDRED GENES
The shapes and relative sizes of
various RNA viruses
The shapes and relative sizes of
various DNA viruses
CHEMICAL COMPOSITION OF
VIRUSES
• Viral nucleic acid
• Viral Proteins
– Structural proteins
– Non-structural proteins
• Viral lipids
• Viral carbohydrates
Viral nucleic acid
• Viral genomes are haploid (contain one copy
of the gene) except the retrovirus genomes
• Either DNA or RNA not both
• NA may be double stranded or single stranded
• May be positive sense or negative (‘minus’)
sense
Genetic Content of Viruses
• DNA viruses:
– Almost all DNA viruses, which infect animals, contain
double-stranded DNA.
– Exceptions include the Parvoviridae (e.g. parvovirus B19,
adeno-associated virus) and the Circoviridae (these include
the recently discovered TT virus, which may be related to
the development of some cases of hepatitis).
• RNA viruses:
– Almost all RNA viruses contain single-stranded RNA.
– Exceptions include the Reoviridae (e.g., rotaviruses) which
contain double-stranded RNA.
– Other RNA viruses can be broadly subdivided as follows:
• Viruses with positive strand (+) RNA genomes
• Viruses with negative strand (-) RNA genomes
• Viruses with positive strand (+) RNA genomes – i.e.,
genomes of the same polarity as mRNA.
– Viruses in this category include picornaviruses and
caliciviruses.
– In addition, retroviruses contain two copies of +RNA,
although they replicate by a unique mechanism.
• Viruses with negative strand (-) RNA genomes – i.e.,
genomes of opposite polarity to mRNA.
– Viruses in this category all have helical capsids.
– Three members of the class are sufficiently closely related
to comprise a distinct taxonomic order – the
Mononegavirales (rhadboviruses, paramyxoviruses and
filoviruses).
– The other (-) strand RNA viruses have segmented genomes
(orthomyxoviruses have 8 segments while arenaviruses and
bunyaviruses have two or three segments respectively
Families of DNA and RNA viruses grouped according
to genome types and pathways for mRNA synthesis
Viral Proteins
• Number of proteins may vary from two (in simple
viruses) to as many as 100 in complex viruses
• Some virus-coded proteins are structural, that is they
form part of the virion e.g. the capsid, protective coat,
ligands for binding to cell receptor molecules
• Others are non-structural proteins, concerned with
regulation of the replication cycle, enzymes e.g.
– transcriptases which transcribe mRNA from dsDNA or
dsRNA viral genomes or from genomes with minus sense
ssRNA
– Reverse transcriptases which transcribes DNA from RNA
found in Retroviruses and Hepadnaviruses
– Other enzymes found in retrovirus particles involved in the
intergration of the transcribed DNA into the cellular DNA
Viral lipids
• Viral envelope is composed of cellular (host)
lipids and viral proteins
• The composition of the lipids of particular
viruses differs according to the composition of
the membrane lipids of the host cells
• Mostly phospholipids
• The proteins occur as virus-coded glycoprotein
spikes embedded within the lipoprotein
bilayer.
Viral carbohydrates
• Occur as oligosaccharide side chains of viral
glycoproteins and glycolipids and as
mucopolysaccharides in enveloped viruses
• More complex viruses may contain internal
glycoproteins or glycosylated outer capsid
proteins
• Since they are usually synthesized by cellular
transferases, their composition corresponds to
that of the host cell.
BACTERIOPHAGES
• Viruses that have bacteria as their hosts or viruses
that infect bacteria
• Importance
– Model systems for virology investigations, the viral life
cycle etc
– Common in all natural environments
– Serious problem in industries, especially where starter
cultures are used, like in the dairy industry
– Used as vectors in molecular biology to transfer genes of
interest
– Identification and epidemiological typing of bacteria
because they are highly host specific
Classification of Bacteriophages
• Morphologically
–
–
–
–
Tailless icosahedral
Icosahedral with contractile tails
Icosahedral with non-contractile tails
Filamentous
• Nucleic acid properties
– DNA or RNA
– Single stranded or double stranded
– Most bacteriophages have ds DNA
• Type of reproductive cycle
– Lytic cycle (Virulent phages)
– Non-lytic cycle, Lysogeny (Lysogenic or temperate phages)
• The temperate phages permit transfer of genes between
bacterial cells, that is, TRANSDUCTION.