The Hashemite University

Department of Medical Laboratory Sciences

Medical Microbiology

An Introduction
to Viruses
By
Lo’ai Alanagreh, PhD

10/21/20 1
 Learning Goals

• You will know when and how viruses were

discovered.
• You will know that there are good and bad
viruses.
• You will be able to answer the question “are
viruses alive”?
• You will understand the defining features and
structure of viruses.
 We Live and Prosper in a Literal
Cloud of Viruses
• Viruses infect all living things.
• We regularly eat, touch and breathe billions
of virus particles.
• We carry viral genomes as part of our own
genetic material.
 How infected are we?

• HSV-1, HSV-2, VZV, EBV …..

• Once infected, it is for life
We Are Viral
Virus Discovery-Filterable Agents
Virus discovery
 What is A Virus?

An infectious, obligate intracellular parasite comprising

genetic material (DNA or RNA) surrounded by a
protein coat and/or an envelope derived from a host
cell membrane
Viruses Are Amazing
 Viral Structure
• Viruses bear no resemblance to cells
– Lack protein-synthesizing machinery
• Viruses contain only the parts needed to invade
and control a host cell
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Capsid

Covering Envelope (not

found in all viruses)
Virus
particle Nucleic acid molecule(s)
(DNA or RNA)
Central
core Matrix proteins
Enzymes (not found in all *
viruses)
 General Structure of Viruses
• Capsids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

– All viruses have capsids

(protein coats that Capsid
enclose and protect their
nucleic acid) Nucleic
acid
– The capsid together with
the nucleic acid is the
nucleocapsid (a) Naked Nucleocapsid
Virus

– Some viruses have an Envelope

external covering called

an envelope; those Spike

lacking an envelope are

Capsi
naked d

– Each capsid is made of Nucleic

acid
identical protein subunits *
called capsomers (b) Enveloped Virus
 General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Two structural Disc

s
capsid types: Capsomers
Nucleic
acid

– Helical -
continuous helix (a)
of capsomers
forming a
cylindrical
nucleocapsid (b)

– Icosahedral Nucleic
acid
Capsid begins
forming helix.

(c) *
 General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Two structural (a) Capsomers

capsid types:
Facet

Capsomers

– Helical - Vertex

– Icosahedral - Nuclei
c
acid

20-sided with 12 (b)

corners
Capsomers

Vertex
Fiber

(c)

*
(d) © Dr. Linda Stannard, UCT/Photo Researchers, Inc.
 General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Viral envelope
– Mostly animal viruses Capsid

– Acquired when the Nucleocapsid

virus leaves the host

Nucleic
acid

cell
© Dennis Kunkel/CNRI/Phototake

(a) (b)

Hemagglutinin spike

– Exposed proteins on Neuraminidase spike

the outside of the Matrix protein

envelope, called Lipid bilayer

spikes, are essential

for attachment of the
virus to the host cell (c)
Nucleocapsid

50 nm

Spikes

Nucleocapsi
d

*
Dr. F. A. Murphy/CDC
(d)
 Functions of Capsid/Envelope
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• Protects the nucleic acid

when the virus is outside
of the host cell

• Helps the virus bind to a

cell surface and assists Capsomers
© Dr. Linda Stannard, UCT/Photo Researchers, Inc.

the penetration of the (a)

Fred P. Williams, Jr./EPA

viral DNA or RNA into a Envelope Capsid DNA core

suitable host cell

*
© Eye of Science/Photo Researchers, Inc.
(b)
 General Structure of Viruses
• Complex viruses: atypical viruses
– 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
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240–300 nm
Nucleic
Core Capsid acid
membrane head
200 nm Collar
Nucleic
acid Sheath
Outer
envelope
Soluble
protein Tail
Lateral
antigens fiber
(a) body s

Tail Base plate

pin
s
(c)

*
(b) © Bin Ni, Chisholm Lab, MIT
 Types of Viruses
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A. Complex Viruses B. Enveloped Viruses

Helical Icosahedral

(1) (3) (5)

(2) (4) (6)

C. Nonenveloped Naked Viruses A. Complex viruses:

(1) poxvirus, a large DNA virus
Helical Icosahedral (2) flexible-tailed bacteriophage

B. Enveloped viruses:
With a helical nucleocapsid:
(3) mumps virus
(4) rhabdovirus
With an icosahedral nucleocapsid:
(5) herpesvirus
(8)
(6) HIV (AIDS)

C. Naked viruses:
Helical capsid:
(7) plum poxvirus
Icosahedral capsid:
(8) poliovirus
*
(7) (9) (9) papillomavirus
 Nucleic Acids
• 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
• 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

*
 General Structure
• Pre-formed enzymes may be present
– Polymerases – DNA or RNA
– Replicases – copy RNA
– Reverse transcriptase – synthesis of DNA
from RNA (AIDS virus)

*
 How Viruses Are Classified
• Main criteria presently used are structure, chemical
composition, and genetic makeup

• Currently recognized: 3 orders, 63 families, and 263

genera of viruses

• Family name ends in -viridae, i.e.Herpesviridae

• Genus name ends in -virus, Simplexvirus

• Herpes simplex virus I (HSV-I)

*
Human Viruses & Viral Diseases

*
*
 Modes of Viral Multiplication
General phases in animal virus multiplication cycle:
1. Adsorption – binding of virus to specific molecules on
the host cell
2. Penetration – genome enters the 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

*
Animal Virus Multiplication
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Host Cell Cytoplasm

Receptors
Cell membrane
Spikes

1 Adsorption. The virus attaches to its

host cell by specific binding of its 1
spikes to cell receptors.

2 Penetration. The virus is engulfed

into a vesicle and its envelope is
3 Uncoated, thereby freeing the viral
RNA into the cell cytoplasm.
2
3

Nucleus

4 Synthesis: Replication and Protein Production.

RNA
Under the control of viral genes, the cell
synthesizes the basic components of new viruses:
RNA molecules, capsomers, spikes.

New
spikes

New
5 Assembly. Viral spike
capsomer
s proteins are inserted into the
5 cell membrane for the viral
New envelope; nucleocapsid is
RNA
formed from RNA and
capsomers.

6 Release. Enveloped viruses bud off

of the membrane, carrying away an 6
envelope with the spikes. This
complete virus or virion is ready to
infect another cell. *
 Adsorption and Host Range
• Virus coincidentally collides with a susceptible host cell and
adsorbs specifically to receptor sites on the 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
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Envelope spike
Host cell membrane
Capsid spike

Receptor

Host cell
membrane

Receptor

*
(a) (b)
 Penetration/Uncoating
• 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

*
Variety in Penetration and Uncoating
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Host cell Free

membrane RNA
Receptors
Uncoating
of
nucleic acid
Receptor- Entry of
spike nucleocapsid
Irreversible Membrane complex
(a) attachment fusion

Uncoating
Host cell step
membrane

Free
Virus in Vesicle, envelope DNA
vesicle and
Specific Engulfmen capsid break down
(b) attachment t

Capsi
d

RNA

Nucleic
acid
Recepto *
r Engulfment into
Adhesion of virus to host Viral RNA is released from
(c)
receptors vesicle vesicle
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
 Release
• Assembled viruses leave the host Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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 (b) © Chris Bjornberg/Photo Researchers, Inc.

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Viral
Host cell nucleocapsid
membrane Viral glycoprotein
spikes
Cytoplasm

Capsid

RN
A

Budding Free infectious

virion virion with *
envelope
Viral matrix
(a) protein
 Damage to Host Cell
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Cytopathic effects - virus-

induced damage to cells
1. Changes in size and shape Normal
cell
Multiple
2. Cytoplasmic inclusion nuclei

bodies
3. Inclusion bodies
Giant
4. Cells fuse to form cell

multinucleated cells
5. Cell lysis (a)
CDC CDC

Inclusion
bodies
6. Alter DNA
7. Transform cells into
cancerous cells

*
© Massimo Battaglia, INeMM CNR, Rome Italy
(b)
Effects of Some Human Viruses

*
 Persistent Infections
• 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

*
 Viral Damage
• Some animal viruses enter the host cell and
permanently alter its genetic material resulting in
cancer – transformation of the cell
• Transformed cells have an increased rate of
growth, alterations in chromosomes, and the
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

*
 Steps in Phage Replication
1. Adsorption – binding of virus to specific
molecules on host cell
2. Penetration – genome enters host cell
3. Replication – viral components are produced
4. Assembly – viral components are assembled
5. Maturation – completion of viral formation
6. Lysis & Release – viruses leave the cell to
infect other cells

*
Multiplication of Bacteriophage
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E. coli
7 Release of viruses
Bacteriophage host

Bacteria Viral
Lysogenic State l DNA
DNA
1 Adsorption

Viral DNA becomes 2 Penetration 6 Lysis of weakened cell

latent as prophage.

Lytic
Cycle

Spliced
DNA viral
splits genome
3 Duplication of phage 5 Maturation
components; replication of
virus genetic material
Viral Bacterial
DNA DNA molecule

Capsid
DNA
The lysogenic state in bacteria.
The viral DNA molecule is inserted at
specific sites on the bacterial
chromosome. The viral DNA is
+
duplicated along with the regular Tail Tail fibers
genome and can provide adaptive 4 Assembly of Sheath
genes for the host bacterium. new virions

Bacteriophage

Bacteriophage assembly line.

First the capsomers are synthesized by the host
cell. A strand of viral nucleic acid is inserted
during capsid formation. In final assembly, the *
prefabricated components fit together into whole
parts and finally into the finished viruses.
Comparison of Bacteriophage and Animal Virus
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Head

Bacterial
cell wall

Tube

Viral nucleic acid

Cytoplas
m
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*
© K.G. Murti/Visuals Unlimited
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
• Why is this property of some viruses so important and
what affect does it have on the spread of some diseases?
*
Lytic and Lysogenic Lifecycles
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E. coli
7 Release of viruses
Bacteriophage host

Bacteria Viral
Lysogenic State l DNA
DNA
1 Adsorption

Viral DNA becomes 2 Penetration 6 Lysis of weakened cell

latent as prophage.

Lytic
Cycle

Spliced
DNA viral
splits genome
3 Duplication of phage 5 Maturation
components; replication of
virus genetic material
Viral Bacterial
DNA DNA molecule

Capsid
DNA
The lysogenic state in bacteria.
The viral DNA molecule is inserted at
specific sites on the bacterial
chromosome. The viral DNA is
+
duplicated along with the regular Tail Tail fibers
genome and can provide adaptive 4 Assembly of Sheath
genes for the host bacterium. new virions

Bacteriophage

Bacteriophage assembly line.

First the capsomers are synthesized by the host
cell. A strand of viral nucleic acid is inserted
during capsid formation. In final assembly, the *
prefabricated components fit together into whole
parts and finally into the finished viruses.
 Lysogeny
• Lysogeny results in the spread of the virus
without killing the host cell
• Phage genes in the bacterial chromosome can
cause the production of toxins or enzymes that
cause pathology – lysogenic conversion
– Corynebacterium diphtheriae
– Vibrio cholerae
– Clostridium botulinum

*
How do we grow viruses?
Obligate intracellular parasites
– what do they need to grow?

They require appropriate cells to

replicate.
 Techniques in Cultivating and
Identifying Animal Viruses
• 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 effects
– Bird embryos – incubating egg is an ideal system; virus
is injected through the shell
– Live animal inoculation – occasionally used when
necessary

*
Methods for Growing Viruses

Inoculation
of amniotic
Inoculation cavity
of embryo
Air sac
Inoculation of
chorioallantoic
membrane

Amnion

Shell Inoculation of
yolk sac
Allantoic
cavity

Albumin
*
(b)
Medical Importance of Viruses
• Viruses are the most common cause of acute
infections
• Several billion viral infections per year
• Some viruses have high mortality rates
• Possible connection of viruses to chronic
afflictions of unknown cause
• Viruses are major participants in the earth’s
ecosystem – How if viruses are not “alive” ?

*
 Detection and Treatment 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)
• Antiviral drugs can cause serious side effects

*
 Prions and Other Infectious Particles
Prions - misfolded proteins, contain no nucleic acid
– Extremely resistant to usual sterilization
techniques
– Cause transmissible spongiform
encephalopathies – fatal neurodegenerative
diseases

*
 Prions Diseases
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Common in animals:
• Scrapie in sheep
and goats Brain cell

• Bovine
Prion
spongiform fibrils

encephalopathies
(BSE), a.k.a. mad
cow disease
© James King-Holmes/Institute of Animal Health/Photo Researchers, Inc.

(a)

• Wasting disease in
elk
• Humans –
Creutzfeldt-Jakob
Syndrome (CJS)
*
Dr. Art Davis/CDC

(b)
Other Noncellular Infectious Agents
• Satellite viruses – dependent on other viruses
for replication
– Adeno-associated virus – replicates only in cells
infected with adenovirus
– Delta agent – naked strand of RNA expressed only
in the presence of hepatitis B virus

• Viroids – short pieces of RNA, no protein coat;

only been identified in plants