Download General structure and classification of viruses

IN THE NAME OF GOD
Department of Microbiology, Islamic Azad
University, Falavarjan Branch
Advanced Virology
Introduction to Virology
By:
Keivan Beheshti Maal
1
HISTORY
The Year 3700 BC
The first written record of a virus
infection consists of a heiroglyph from
Memphis, the capital of ancient Egypt
Showing a temple priest, Ruma, with
clinical signs of Paralytic Poliomyelitis
2
HISTORY
The Year 1193 BC
The Pharaoh Siptah rules Egypt from 1200-1193 BC
when he dies suddenly at the age of about 20
His mummified body lays undisturbed in his tomb in the
Valley of the Kings until 1905 when the tomb was
excavated.
The mummy shows that his left leg was withered and his foot was
rigidly extended like a horse's hoof
.
classic paralytic poliomyelitis
FOOT
3
HISTORY
The Year 1143 BC
Ramesses V's preserved mummy shows that he
died of smallpox at about the age of 35 in 1143 BC
The pustular lesions on the face of the mummy are
very similar to those of more recent patients
However, his head also displays a major wound
inflicted either before or shortly after death
4
HISTORY
The Year 1000 BC
Smallpox is endemic in China by 1000BC
[In response, the practice of variolation is developed]
Variolation:
1) inhalation of the dried crusts from smallpox lesions
2) inoculation of the pus from a lesion into a scratch on the forearm
5
HISTORY
The Year 1520
Smallpox
710: reached Europe from the East
1520: reached the Americas by Hernando Cortez
3,500,000 Aztecs died in the next 2 years
6
HISTORY
1796: Edward Jenner
vaccinated an 8 year old boy, James Phipps, with material
from a cowpox lesion on the hand of Sarah Nelmes
James developed a small lesion at the site of vaccination
which healed in 2 weeks
On 1st July 1796, Jenner challenged the boy by
inoculating him with material from a real case of smallpox
1798: Edward Jenner
introduced the term virus in microbiology
[Virus in Greek = poison]
The boy developed sustained immunity against smallpox.
7
HISTORY
1886: John Buist (Scottish pathologist)
Staining of skin lesions of a smallpox patient
[ saw "elementary bodies" which he thought were the spores of
micrococci]
smallpox virus particles - just large enough in light microscope
1892: Dmitri Iwanowski (Russian botanist)
Submission a paper in the St. Petersburg Academy of Science:
[extracts from diseased tobacco plants can transmit disease to other
plants after passage through ceramic filters fine enough to retain the
smallest known bacteria]
*Beginning of Virology*
.
8
HISTORY
1851-1902: Walter Reed
1) Yellow fever was caused by a virus (1900)
2) Spread by mosquitoes
1868-1943: Karl Landsteiner and Erwin Popper
poliomyelitis was caused by a virus
First scientists to prove:
[viruses could infect humans as well as animals]
9
HISTORY
1879-1970: Francis Peyton Rous
Rous sarcoma virus can cause cancer in chickens
(For this work, was awarded the Nobel Prize in 1966)
First person to show:
[ a virus could cause cancer in animals]
1873-1949: Felix d'Herelle
Following Frederick Twort's independently recognized
viruses which infect bacteria, which he calls
bacteriophages (eaters of bacteria).
The discovery of bacteriophages provided an invaluable
opportunity to study virus replication at a time prior to
the development of cell culture when the only way to
study viruses was by infecting whole organisms
10
HISTORY
1887-1955: Wendell Stanley
Crystallized Tobacco Mosaic Virus (TMV) & showed
that it remained infectious (Nobel Prize, 1946)
The first step towards describing the molecular
structure of any virus
1899-1972: Max Theiler
Propagate yellow fever virus in chicken embryos and
successfully produced an attenuated vaccine
[Theiler's vaccine was so safe and effective that it is still
in use today]
1) Saved millions of lives
2) Set the model for the production of many subsequent
vaccines
(Nobel Prize in 1951)
11
HISTORY
Emory Ellis (1906-) and Max Delbrück (1906-1981)
1939: Established "one step virus growth cycle"
1) Essential to the understanding of virus replication
2) virus particles do not "grow" but are instead assembled
from preformed components
1941: George Hirst
influenza virus agglutinates red blood cells
This was the first rapid, quantitative method of
measuring eukaryotic viruses
Now viruses could be counted!
12
HISTORY
Salvador Luria (1912-1991)
1945: bacteriophages mutate
(Nobel Prize, 1969)
Alfred Hershey (1908-1997)
1) similar genetic mechanisms operate in viruses
as in cellular organisms
2) basis for the understanding of antigenic
variation in viruses.
13
HISTORY
John Enders (1897-1985)
Thomas Weller (1915–)
Frederick Robbins (1916–)
1949: Grow poliovirus in vitro using human tissue culture.
(Nobel Prize, 1954)
This development led to the isolation of many new viruses in tissue
culture
14
HISTORY
1950: André Lwoff, Louis Siminovitch and Niels Kjeldgaard
Discovery of lysogenic bacteriophages in Bacillus megaterium
(Nobel Prize, 1965).
1) Clarified the existence of temperate and virulent bacteriophages
2) Control of gene expression in prokaryotes
1950: World Health Organization proposed a program to eradicate
smallpox from the Americas [Achieved in 8 years]
1952: Renato Dulbecco
Animal viruses can form plaques in a similar way to bacteriophages
(Nobel Prize, 1975)
[Rapid quantification of animal viruses using plaque assay like phages]
15
HISTORY
1957: Alick Isaacs and Jean Lindemann
Discovery of interferon.
[interferons were the first cytokines to be studied in detail]
1963: Baruch Blumberg
Discovery of Hepatitis B Virus (HBV)
(Nobel Prize, 1976)
Howard Temin
1970 David Baltimore 
independently
Discovery of
reverse transcriptase in retroviruses
(Nobel Prize, 1975)
16
HISTORY
1976: Michael Bishop and Harold Varmus
discovered that the oncogene from Rous sarcoma virus is also found in
the cells of normal animals, including humans (Nobel Prize, 1989)
1983: Luc Montaigner and Robert Gallo announced the
Discovery of human immunodeficiency virus (HIV), the causative agent of
AIDS
[only two years after starting AIDS epidemic]
1999: Largest virus genome Paramecium bursaria Chlorella virus 1
Sequencing
2001: Publication of complete nucleotide sequence of human genome
About 11% of the human genome is composed of retrovirus-like
retrotransposons
17
The Viruses
 General Characteristics
Size, Shape, Classification,
Composition (NA, protein, lipid)
Infectivity (Host range & tissue tropism)
 Replication
Phages vs Animal viruses
DNA viruses vs RNA viruses
 Effects on Cells
Cytopathology, Organismal effects
Oncogenes and tumorigenesis
18
General characteristics of viruses
 Viruses are smaller than bacteria, they range in size
between 20-300 nanometer.
 Viruses contain only one type of nucleic acid, either
DNA or RNA, but never both.
 Viruses consist of nucleic acid surrounded by a protein
coat. Some viruses have additional lipoprotein envelope.
 Viruses lack cellular organelles, such as mitochondria
and ribosomes.
19
E. coli T- phages
20
Perspective Size:
21
22
Sizes of microscopic and submicroscopic biological entities
Sizes of microscopic and submicroscopic biological entities
and
andtheir
theirability
abilitytotobebeexamined
examinedusing
usingvarious
varioustechnologies
technologies
Flint et al., 2004, Principles of Virology, Fig. 1.8
23
General characteristics of viruses
 Viruses are obligate cellular parasites.
[replicate only inside living cells]
 Viruses replicate through replication of their nucleic
acid and synthesis of the viral protein.
 Viruses do not multiply in chemically defined media
 Viruses do not undergo binary fission
24
Shape of Viruses
 Spherical
 Rod-shaped
 Brick-shaped
 Tadpole-shaped
 Bullet-shaped
 Filament
25
Shapes of Viruses:Spherical
26
Shapes of Viruses :Rod-shaped
27
Shapes of Viruses :Brick-shaped
.
28
Shape of Viruses: Tadpole-shaped
29
Shapes of Viruses :Bullet-shaped
30
Shapes of Viruses :Filament
31
Symmetry of viruses
Viruses are divided into three groups, based on the
morphology of the nucleocapsid and the
arrangement of capsomeres.
 1-Cubic symmetry:
The virus particle is icosahedral in shape (almost
spherical particle ) and the nucleic acid contained
inside the capsid. The icosahedron particle is
composed of 20 equilateral triangles , 12 vertices
and has 2,3,5 rotational symmetry.
32
Cubic symmetry
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33
Symmetry of viruses
 2- helical symmetry :
The virus particle is elongated or pleomorphic (not spherical),
and the nucleic acid is spiral. Caposomeres are arranged
round the nucleic acid.
 3- complex symmetry:
The virus particle does not confirm either cubic or helical
symmetry.
34
(d) Helical
Virus Symmetry
35
Virus Symmetry
36
HELICAL ICOSAHEDRAL
37
(e) Icosahedral
Virus Symmetry
38
Virus Symmetry
39
Terminology
 Virion: The complete virus particle (infectious form)
 Capsid: The protein coat that surrounds nucleic acid.
 Nucleocapsid: The nucleic acid plus the capsid.
 Capsomeres: The structural protein units that made up the
capsid.
 Defective virus: the virus cannot replicate by its own, it
requires helper virus.
40
Function of Virion Proteins
41
Principles of Virology 2004 2nd edition , Flint, S.J. et al.
Virion
nucleocapsid
envelope
enveloped
virus
capsomeres
A virion
Nucleocapsid
(a nucleocapsid without
a genome is a capsid)
42
Basic virus structure
43
Basic virus structure
http://www.med.sc.edu:85/mhunt/intro-vir.htm
From Medical Microbiology, 5th ed., Murray, Rosenthal &
Pfaller, Mosby Inc., 2005, Fig. 6-5.
44
Enveloped helical virus
Enveloped icosahedral virus
45
Viruses with Envelopes
 The capsid is surrounded by a lipid envelope
 Virus particles possess an envelope formed by a viral glycoprotein-
containing membrane derived from the host cell.
 Components
 Viral envelopes is a lipid membrane acquired from the host cell
during assembly.
 The great majority of viral protein (embedded in the membrane) are
glycoproteins that carry covalently linked sugar chains or
oligosaccharides
Herpesvirus
46
Viral glycoproteins are oligomers
47
A Typical Viral Envelope Glycoprotein
N-linked
oligosaccha
rides
Disulfide bonds
Principles of Virology 2004 2nd edition , Flint, S.J. et al.
48
The Hemagglutinin (HA) Protein of Human
Influenza A Virus
 The HA protein is a trimer of disulfide-linked HA1 and
HA2 molecules
 Mediate attachment to and entry of these virus
particles into a host cell
49
Principles of Virology 2004 2nd edition , Flint, S.J. et al.
The Hemagglutinin (HA) Protein of Human
Influenza A Virus
50
Virion Enzyme
Many types of virus particle contain enzymes necessary 
for synthesis of viral nucleic acids within an infected cell.
51
Principles of Virology 2009 2nd edition , Flint, S.J. et al.
52
General structure of viruses
 Viruses composed of nucleic acid either DNA or RNA, surrounded
by a protein coat called the capsid.
 The capsid is composed of small structural units called capsomeres.
 The capsid protects nucleic acid from inactivation by the outer
physical conditions.
 Some viruses have additional lipoprotein envelope composed of
virally coded protein and host lipid.
 The viral envelope is covered with glycoprotein spikes.
53
Classification Parameters
 Several Parameters Are Used for Classification
Viral classification study is referred to as Taxonomy
 73 families exist so far
 Type of genomic nucleic acid
 Size of virion and genome
 Capsid structure
 Host
 Replication mechanism
54
ICTV Classification System
Viral classification starts at the level of order and follows
as thus, with the taxon suffixes given in italics:
 Order (-virales)
 Family (-viridae)
 Subfamily (-virinae)
 Genus (-virus)
 Species (-virus)
Names of orders and families are italicized.
Species names generally take the form of [Disease]
Virus.
Recognition of orders very recent and deliberately slow;
to date, only three have been named, and most families
remain unplaced.
Approximately 80 families and 4000 species of virus are
known.
55
DNA
Single Stranded
Double Stranded
VIRUS
GENOMES
RNA
+ or -
Segmented
Double Stranded Segmented
Circular
56
DNA
double-stranded
line
ar
circular
singl sing
e
le
RNA
single-stranded
line
ar
circular
multip singl sing
le
e
le
multip
le
doublestranded
single-stranded
linear
linear (circular)*
singl
e
multipl
e
(+)sense
sing
le
multip
le
(-)sense
sing
le
multip
le
57
58
Classification of Human Viruses
Group
Family
Genome
Genome size
Capsid Envelope
(kb)
dsDNA
Poxviridae
dsDNA, linear
130 to 375
Complex
Yes
Herpesviridae
dsDNA, linear
124 to 325
Icosahedral Yes
Adenoviridae
dsDNA, linear
36 to 38
Icosahedral No
Polyomaviridae dsDNA, circular
5.0
Icosahedral No
PapillomaviridaedsDNA, circular
8.0
Icosahedral No
Parvoviradae
5.0
Icosahedral No
Hepadnaviridae dsDNA (partial), circular
3.2
Icosahedral Yes
Retroviridae
7 to 11
Icosahedral Yes
ssDNA
ssDNA, linear, (- or +/-)
Retro
ssRNA (+), diploid
59
Classification of Human Viruses
Group
Family
Genome
ssRNA (+)
Genome size Capsid Envelope
(kb)
Picornaviridae
ssRNA (+)
7.2 to 8.4
Icosahedral No
Noroviridae
ssRNA (+)
7.2 to 7.9
Icosahedral No
Coronaviridae
ssRNA (+)
20 to 30
Helical
Yes
Flaviviridae
ssRNA (+)
9.5 to 12.5
Spherical
Yes
Togaviridae
ssRNA (+)
9.7 to 11.8
Spherical
Yes
Filoviridae
ssRNA (-)
19.1
Helical
Yes
Paramyxoviridae ssRNA (-)
16 to 20
Helical
Yes
Rhabdoviridae
13 to 16
Helical
Yes
10 to 13.6
Helical
Yes
ssRNA (-)
ssRNA (-)
OrthomyxoviridaessRNA (-), segmented
Bunyaviridae
ssRNA (-, ambi), segmented11 to 21
Helical
Yes
Arenaviridae
ssRNA (-, ambi), segmented10 to 14
Helical
Yes
Reoviridae
dsRNA, segmented
Icosahedral No
dsRNA
16 to 27
60
Size of Viruses
 Ranges of sizes
 20 nm to 500 nm (spherical)
 12 nm to 300-2000 nm (rod like)
 Easily observed
 with electron microscope
 Ex.1 Mimivirus is 500 nm
 Infects algae
 Ex.2 Parvovirus is 20 nm in diameter
 Infects algae
 Viral genomes range in size 2,000 bp to 1,200,000 bp
61
62
Under attack!
(From Medical Microbiology, 4th ed., Murray, Rosenthal, Kobayashi & Pfaller, Mosby Inc., 2002, Fig. 65-1.)
63
Structures compared
From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-4.
64
Baltimore classification
 Group I: double-stranded DNA viruses e.g. Herpesviridae – HSV 1 & 2, EBV
 Group II: single-stranded DNA viruses e.g. Parvoviridae – Parvovirus B19
 Group III: double-stranded RNA viruses e.g. Reoviridae - Rotavirus
 Group IV: positive-sense single-stranded RNA viruses e.g. Picornaviridae –
Poliovirus, Hepatitis A virus; Coronaviridae - SARS
 Group V: negative-sense single-stranded RNA viruses e.g. Paramyxoviridae –
Measles virus; Filoviridae – Ebola virus
 Group VI: reverse transcribing Diploid single-stranded RNA viruses e.g.
Retroviridae – HIV, HTLV 1 & 2
 Group VII: reverse transcribing Circular double-stranded DNA viruses e.g.
Hepadnaviridae – Hepatitis B virus
65
Baltimore classification
Viruses were divided into six groups based on the their nucleic acid
and m-RNA production.
 1- ds-DNA viruses.
 2- ss-DNA viruses.
 3- ds- RNA viruses.
 4- ss-RNA viruses with positive strands( positive polarity).
 5- ss-RNA viruses with negative strands(negative polarity).
 6- ss-RNA viruses associated with the enzyme reverse transcriptase.
 7- ds-DNA viruses associated with the enzyme reverse transcriptase
Circular double-stranded DNA viruses e.g. Hepadnaviridae –
Hepatitis B virus
66
1- Double stranded DNA families of medical
importance





1- Poxviridae.
2- Herpesviridae.
3- Hepadnaviridae.
4- Adenoviridae.
5- Papovaviridae.
67
2- Single stranded DNA families.
3- Double stranded RNA families.
 Single stranded DNA family:
1- Parvovoridae.
 Double stranded RNA family:
1- Reoviridae.
68
4- Single stranded RNA families with positive strands
 The viral genome acts directly as m-RNA.






1- Picornaviridae.
2- Caliciviridae.
3- Astroviridae.
4- Coronaviridae.
5- Flaviviradae.
6- Togaviridae.
69
5- Single stranded RNA families with negative strands
 The viral genome does not act as m-RNA.
 It must be transcribed by the viral enzyme transcriptase
into m-RNA.
 Virions contain the enzyme transcriptase.




1- Orthomyxoviridae.
2- Paramyxoviridae.
3- Rhabdoviridae.
4- Filoviridae.
70
6-Single stranded RNA viruses associated with the
enzyme reverse transcriptase
 The
viral genome is reverse transcribed into a
complementary DNA strand using the enzyme reverse
transcriptase.
 Retroviridae.
71
The Viruses
Replication
Phages:
Lytic vs lysogenic infection, Transduction
Animal viruses:
DNA viruses vs RNA viruses, Retroviruses
72
Replication Cycle of Animal Viruses
 animal virus reproduction can be compared with
reproduction of bacteriophage with a few
additional steps
1. attachment
2. entry : the entire virus enters the host cell
3. targeting (usually the nucleus)
4. uncoating: the nucleic acid separates from the
capsid
5. replication of nucleic acid and protein
6. maturation
73
Replication Cycle of Animal Viruses
7. release
 host cells often die due to lack of functioning DNA and
the ability to function as needed. Cells lyse when they
die, releasing the viruses.
 budding is a process of releasing the virus that does not
necessarily kill the host cell
8. shedding outside of host
 usually use the same openings or surfaces used to gain
entrance into the host
9. transmission to next host
 enters the new host and the infection cycle begins again
74
75
Virus replication: general
76
Virus replication:
variations on the theme
 dsDNA
 ssDNA
 (+)ssRNA
 (-)ssRNA
 dsRNA
 RNA retro
 DNA retro
77
dsDNA virus replication
(+)mRNA
dsDNA
dsDNA
78
ssDNA virus replication
(+)mRNA
(+)
ssDNA
dsDNA
79
(+)ssRNA virus replication
(+)RNA
(-)RNA
(+)RNA
80
(-)ssRNA virus replication
(+)mRNA
(-)RNA
(+)RNA
(-)RNA
81
dsRNA virus replication
dsRNA
(+)mRNA
dsRNA
82
(+)ssRNA retrovirus replication
(+)mRNA
(+)RNA
dsDNA
ssDNA
(+)RNA
83
dsDNA retrovirus replication
(+)mRNA
dsDNA
dsDNA
(+)RNA
ssDNA
84
What phages do to Host Cell
85
Lytic Life Cycle
86
General
Phage
Life
Cycle
87
Lytic
vs
Lysogenic
Cycle
88
Transduction
89
Transduction
90
91
Information
Flow in
Different
Viruses
92
Replication:
A DNA Virus
93
Replication:
An RNA Virus
94
Penetration
95
Penetration:
HIV virus
96
Biosynthesis:
HIV virus
97
Release
98