5. introduction to viruses

Program PGMIPABI
Fakultas Keguruan dan Ilmu Pendidikan
Universitas Syiah Kuala

An Introduction to the Viruses

History (1)

• For many years, the cause of viral infections such as
smallpox and polio was unknown, even though it was
clear that the diseases were transmitted from person to
person.
• The French bacteriologist Louis Pasteur was certainly on the right
track when he postulated that rabies was caused by a “living
thing” smaller than bacteria,
• in 1884 he was able to develop the first vaccine for rabies.
• Pasteur also proposed the term virus to denote this special
group of infectious agents.

Program PGMIPABI-FKIP Unsyiah

History (2)

• The first substantial revelations about the unique
characteristics of viruses occurred in the 1890s.
• First, D. Ivanovski and M. Beijerinck showed that a disease in
tobacco was caused by a virus (tobacco mosaic virus).
• Friedrich Loeffler and Paul Frosch discovered a virus that causes
foot-and-mouth disease in cattle.
• These early researchers found that when infectious
fluids from host organisms were passed through
porcelain filters designed to trap bacteria, the filtrate
remained infectious.


History (3)

• Over the succeeding decades, a remarkable picture of
the physical, chemical, and biological nature of viruses
began to take form.
• Years of experimentation were required to show that
viruses were noncellular particles with a definite size,
shape, and chemical composition.
• Using special techniques, they could be cultured in the
laboratory.
• By the 1950s, virology had grown into a multifaceted discipline
that promised to provide much information on disease, genetics,
and even life itself


The Position of Viruses in the Biological
Spectrum

• Viruses are a unique group of biological entities known
to infect every type of cell, including bacteria, algae,
fungi, protozoa, plants, and animals.
• it is best to describe viruses as infectious particles
(rather than organisms) and as either active or inactive
(rather than alive or dead).
• Viruses are different from their host cells in size,
structure, behavior, and physiology.
• They are a type of obligate intracellular parasite that cannot
multiply unless it invades a specific host cell and instructs its
genetic and metabolic machinery to make and release quantities
of new viruses.


Properties of Viruses


General Structure of Viruses

• As a group, viruses represent the smallest
infectious agents.
• Their size places them in the realm of the
ultramicroscopic .
• This term means that most of them are so minute (<0.2 μm)
that an electron microscope is necessary to detect them or
to examine their fine structures.


The Size of Viruses

Size comparison of viruses with a eukaryotic cell (yeast) and bacteria. Viruses range from largest (1) to smallest
(9). A molecule of a large protein (10) is included to indicate proportion of macromolecules.

Viral Components: Capsids, Nucleic Acids,
and Envelopes (1)

• The general plan of virus organization is the
utmost in simplicity and compactness.
• Viruses contain only those parts needed to
invade and control a host cell:
• an external coating and a core containing one or more
nucleic acid strands of either DNA or RNA.


Viral Components: Capsids, Nucleic Acids,
and Envelopes (2)


Capsids (1)

• All viruses have capsids - protein coats that
enclose and protect their nucleic acid.
• Each capsid is constructed from identical
subunits called capsomers made of protein.
• The capsid together with the nucleic acid are
nucleoscapsid.
• Some viruses have an external covering called
envelope; those lacking an envelope are
naked.


Capsids (2)

Generalized structure of viruses. (a) The simplest virus is a naked virus (nucleocapsid) consisting of a geometric
capsid assembled around a nucleic acid strand or strands. (b) An enveloped virus is composed of a nucleocapsid
surrounded by a flexible membrane called an envelope. The envelope usually has special receptor spikes inserted into
it.


Capsids (3)

• Two structural types:
• helical - continuous helix of capsomers forming a
cylindrical nucleocapsid
• The nucleocapsids of naked helical viruses are very rigid and tightly
wound into a cylinder-shaped package. Ex: TMV
• Enveloped helical nucleocapsids are more flexible and tend to be
arranged as a looser helix within the envelope. Ex: influenza,
measles, and rabies viruses
• icosahedral - 20-sided with 12 corners
• vary in the number of capsomers
• a poliovirus has 32, and an adenovirus has 242 capsomers
• Each capsomer may be made of 1 or several proteins.


Helical capsids

Typical variations of viruses with helical nucleocapsids. Naked helical virus (tobacco mosaic virus):
(a) a schematic view and (b) a greatly magnified micrograph. Note the overall cylindrical morphology.
Enveloped helical virus (influenza virus): (c) a schematic view and (d) a colorized micrograph featuring a
positive stain of the avian influenza virus. This virus has a well-developed envelope with prominent spikes
termed H5N1 type.


Icosahedral viruses (1)


Icosahedral viruses (2)

Two types of icosahedral viruses, highly magnified. (a) Upper view: A negative stain of rotaviruses
with unusual capsomers that look like spokes on a wheel; lower view is a three
dimensional model of this virus. (b) Herpes simplex virus, a type of enveloped icosahedral virus.

Viral envelope

• When enveloped viruses (mostly animal) are released from the
host cell, they take with them a bit of its membrane system in the
form of an envelope.
• Some viruses bud off the cell membrane; others leave via the
nuclear envelope or the endoplasmic reticulum.
• Some proteins form a binding layer between the envelope and
capsid of the virus, and glycoproteins (proteins bound to a
carbohydrate) remain exposed on the outside of the envelope.
• These protruding molecules, called spikes or peplomers, are
essential for the attachment of viruses to the next host cell.


Functions of Capsid/Envelope

• The outermost covering of a virus is
indispensable to viral function
• it protects the nucleic acid from the effects of various
enzymes and chemicals when the virus is outside the
host cell.
• Capsids and envelopes are also responsible for helping
to introduce the viral DNA or RNA into a suitable host
cell,
• by binding to the cell surface
• by assisting in penetration of the viral nucleic acid


Complex viruses: atypical viruses (1)

• Two special groups of viruses, termed complex viruses
are more intricate in structure than the helical,
icosahedral, naked, or enveloped viruses just described.
• Poxviruses lack a typical capsid and are covered by a
dense layer of lipoproteins.
• Some bacteriophages have a polyhedral nucleocapsid
along with a helical tail and attachment fibers.


Complex viruses: atypical viruses (2)

Detailed structure of complex viruses. (a) Section through the vaccinia virus, a poxvirus, shows its
internal components. (b) Photomicrograph and (c) diagram of a T4 bacteriophage.

Basic types of viral morphology

A. Complex viruses: (1) poxvirus, a large DNA virus (2) flexible-tailed bacteriophage
B. Enveloped viruses:
• With a helical nucleocapsid: (3) mumps virus(4) rhabdovirus
• With an icosahedral nucleocapsid: (5) Herpesvirus (6) HIV (AIDS)
C. Naked viruses:
• Helical capsid: (7) plum poxvirus
• Icosahedral capsid: (8) Poliovirus ; (9) papillomavirus


Nucleic acids (1)

• Viral genome – either DNA or RNA but never
both
• Carries genes necessary to invade host cell and
redirect cell’s activity to make new viruses
• Number of genes varies for each type of virus –
few to hundreds


Nucleic acids (2)

• DNA viruses
• usually double stranded (ds) but may be single stranded
(ss)
• circular or linear
• RNA viruses
• usually single stranded, may be double stranded, may be
segmented into separate RNA pieces
• ssRNA genomes ready for immediate translation are
positive-sense RNA.
• ssRNA genomes that must be converted into proper form
are negative-sense RNA.


Other Substances in the Virus
Particle

• In addition to the protein of the capsid, the proteins and lipids of
envelopes, and the nucleic acid of the core, viruses can contain
enzymes for specific operations within their host cell.
• They may come with preformed enzymes that are required for viral
replication.
• polymerases that synthesize DNA and RNA and replicases that copy
RNA.
• The AIDS virus comes equipped with reverse transcriptase for
synthesizing DNA from RNA.
• However, viruses completely lack the genes for synthesis of
metabolic enzymes.
• this deficiency has little consequence, because viruses have adapted to
assume total control over the cell’s metabolic resources.


How Viruses Are Classified and
Named (1)

• Classified based on structures, size, nucleic acids,
host species, target cells.
• 3 orders, 63 families, and 263 genera of viruses
• Family name ends in -viridae
• Genus name ends in -virus, Simplexvirus,
Hantavirus, Enterovirus
• Name of genus or family begins with description of
virus
• appearance: togavirus, coronavirus
• place collected: adenovirus, hantavirus
• effect on host: lentivirus
• acronymns: picornavirus; hepadnavirus


How Viruses Are Classified and
Named (2)


DNA VIRUS


RNA VIRUS


Modes of Viral Multiplication (1)

• General phases in animal virus multiplication cycle:
1. Adsorption - binding of virus to specific molecule
on host cell
2. Penetration - genome enters host cell
3. Uncoating – the viral nucleic acid is released from
the capsid
4. Synthesis – viral components are produced
5. Assembly – new viral particles are constructed
6. Release – assembled viruses are released by
budding (exocytosis) or cell lysis


Modes of Viral Multiplication (2)

General features in the multiplication cycle
of an enveloped animal virus. Using an RNA
virus (rubella virus), the major events are
outlined, although other viruses will vary in
exact details of the cycle.


Adsorption and Host Range (1)

• Virus coincidentally collides with a susceptible
host cell and adsorbs specifically to receptor
sites on the cell membrane
• Spectrum of cells a virus can infect – host
range
• hepatitis B – human liver cells
• poliovirus – primate intestinal and nerve cells
• rabies – various cells of many mammals


Adsorption and Host Range (2)

The mode by which animal viruses adsorb to the host cell membrane. (a) An enveloped
coronavirus with prominent spikes. The configuration of the spike has a complementary fit for cell
receptors. The process in which the virus lands on the cell and plugs into receptors is termed docking.
(b) An adenovirus has a naked capsid that adheres to its host cell by nestling surface molecules on its
capsid into the receptors on the host cell’s membrane.

Penetration/Uncoating (1)

• Flexible cell membrane is penetrated by the
whole virus or its nucleic acid by:
• endocytosis – entire virus is engulfed and
enclosed in a vacuole or vesicle
• fusion – envelope merges directly with membrane
resulting in nucleocapsid’s entry into cytoplasm


Penetration/Uncoating (2)

Two principal means by which animal viruses penetrate. (a) Endocytosis (engulfment) and
uncoating of a herpesvirus. (b) Fusion of the cell membrane with the viral envelope (mumps virus).

Replication and Protein Production

• Varies depending on whether the virus is a DNA or RNA
virus
• DNA viruses generally are replicated and assembled in
the nucleus.
• RNA viruses generally are replicated and assembled in
the cytoplasm.
• Positive-sense RNA contain the message for translation.
• Negative-sense RNA must be converted into positive-sense
message.


Assembly: Filling the capsid

• Capsid proteins made in cytoplasm
• DNA or RNA gets fills empty capsids
• final modifications to capsid
• to plug any holes from DNA/RNA entry
• to mature the outer proteins


Release (1)

• Assembled viruses leave host cell in one of two ways:
• budding – exocytosis; nucleocapsid binds to membrane
which pinches off and sheds the viruses gradually; cell is
not immediately destroyed
• lysis – nonenveloped and complex viruses released when
cell dies and ruptures
• A fully formed, extracellular virus particle that is virulent
(able to establish infection in a host) is called a virion
• Number of viruses released is variable
• 3,000-4,000 released by poxvirus
• >100,000 released by poliovirus


Release (2)

Maturation and release of enveloped viruses. As parainfluenza virus is budded off the membrane, it
simultaneously picks up an envelope and spikes.


Damage to Host Cell

• Cytopathic effects - virus-induced damage to
cells
1. Changes in size & shape
2. Cytoplasmic inclusion bodies
3. Nuclear inclusion bodies
4. Cells fuse to form multinucleated cells.
5. Cell lysis
6. Alter DNA
7. Transform cells into cancerous cells


Persistent Infections (1)

• Persistent infections - cell harbors the virus
and is not immediately lysed
• Can last weeks or host’s lifetime; several can
periodically reactivate – chronic latent state
• measles virus – may remain hidden in brain cells for
many years
• herpes simplex virus – cold sores and genital herpes
• herpes zoster virus – chickenpox and shingles


Persistent Infections (2)

• Some animal viruses enter host cell and
permanently alter its genetic material resulting in
cancer – transformation of the cell.
• Transformed cells have increased rate of growth,
alterations in chromosomes, and capacity to divide
for indefinite time periods resulting in tumors.
• Mammalian viruses capable of initiating tumors are
called oncoviruses.
• Papillomavirus – cervical cancer
• Epstein-Barr virus – Burkitt’s lymphoma


Multiplication Cycle in
Bacteriophages

• Bacteriophages – bacterial viruses (phages)
• Most widely studied are those that infect Escherichia coli
– complex structure, DNA
• Multiplication goes through similar stages as animal
viruses.
• Only the nucleic acid enters the cytoplasm - uncoating is
not necessary.
• Release is a result of cell lysis induced by viral enzymes
and accumulation of viruses - lytic cycle.


6 Steps in Phage Replication

1. Adsorption – binding of virus to specific molecule on
host cell
2. Penetration –genome enters host cell
3. Replication – viral components produced
4. Assembly - viral components assembled
5. Maturation – completion of viral formation
6. Release – viruses leave cell to infect other cells


Penetration & Release of Phage

Penetration of a bacterial cell by a T-even bacteriophage and A weakened bacterial cell, crowded with viruses.


Lysogeny: The Silent Virus Infection

• Not all phages complete the lytic cycle.
• Some DNA phages, called temperate phages, undergo
adsorption and penetration but don’t replicate.
• The viral genome inserts into bacterial genome and
becomes an inactive prophage - the cell is not lysed.
• Prophage is retained and copied during normal cell
division resulting in the transfer of temperate phage
genome to all host cell progeny – lysogeny.
• Induction can occur resulting in activation of lysogenic
prophage followed by viral replication and cell lysis.


Techniques in Cultivating and
Identifying Animal Viruses (1)

• Obligate intracellular parasites that require
appropriate cells to replicate
• Methods used:
• cell (tissue) cultures – cultured cells grow in sheets
that support viral replication and permit observation for
cytopathic effect
• bird embryos – incubating egg is an ideal system;
virus is injected through the shell
• live animal inoculation – occasionally used when
necessary



Cell Culture



Cultivating animal viruses in a developing bird embryo


Detection of Animal Viral Infections

• More difficult than other agents
• Consider overall clinical picture
• Take appropriate sample
• Infect cell culture – look for characteristic
cytopathic effects
• Screen for parts of the virus
• Screen for immune response to virus
(antibodies)


Diagnosis


Treatment of viral infections

• The nature of viruses has at times been a major impediment to effective therapy.
• Because viruses are not bacteria, antibiotics aimed at bacterial infections do not
work.
• While there are increasing numbers of antiviral drugs, most of them block
virus replication by targeting the function of host cells. This can cause severe side
effects.
• Antiviral drugs are designed to target one of the steps in the viral life cycle you
learned about earlier in this chapter.
• Azidothymide (AZT), a drug used to treat AIDS, targets the nucleic acid synthesis
stage.
• A newer class of HIV drugs, the protease inhibitors, disrupts the final assembly
phase of the viral life cycle.
• Another compound that shows some potential for treating and preventing viral
infections is a naturally occurring human cell product called interferon
• Vaccines that stimulate immunity are an extremely valuable tool but are
available for only a limited number of viral diseases


Important viruses you should know…

• Smallpox (variola major, minor) – complex virus;
inclusions
• Herpesviridae – (herpes; chicken pox – varicella zoster);
chronic latent state  reactivated; nuclear inclusions
• HPV – can transform cells; warts  cervical cancer
• Hepatovirus (A, B, C)
• SARS – coronavirus (like the virus that causes
bronchitis); prominent spikes on envelope
• influenza – Flu; Type A is the one you’ve had;
• Rotavirus – viral food poisoning; vomiting and diarrhea –
sometimes concurrently!!
• HIV – retrovirus; latency;


THANK YOU


5. introduction to viruses

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