STRUCTURE OF VIRUS

Dr Sobia Kanwal
 STRUCTURE OF VIRUS
 Viruses are not plants, animals, or bacteria, but they are the
quintessential parasites of the living kingdoms
 Viruses are small compared to the wavelength of visible light; indeed,
while the largest virus can be discerned in a good light microscope,
 the vast majority of viruses can only be visualized in detail using an
electron microscope.
 The size of a virus is comparable to that of a large protein
macromolecule, ranging from 0.2 to 2 μm
Size of Virus
The size of viruses
Size Comparision with other
organisim
 The Structure Of a Virus
 Viruses are composed of a
core of nucleic acid
 The Nucleic acid core is
surrounded by a protein coat
called a capsid
 The Nucleic core is either
made up of DNA or RNA
but never both
 Some are enclosed by an
envelope
 Some viruses have spikes
 Structures compared

From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-4.
Organization of Viral Particles

Contains RNA or DNA

Form a protective package
Transmit genetic material
Entry, multiply and exit

the host
Redirect cellular machinery
Basic viral intra structure
Basic viral intra structure
 VIRUS STRUCTURE
 Basic rules of virus architecture, structure, and assembly
are the same for all families
 Some structures are much more complex than others, and
require complex assembly and disassembly
 Virus are simple structure consisting of:

1. Capsid:
• regular, shell-like structure composed of aggregated
protein subunits which surrounds the viral nucleic acid.
 Viral Capsid ….
• Provides the virus with its shape
• Makes up 95% of a virus’s size
• They may be
– Rod-shaped
– Polyhedral
– More complex
• Capsids are built from large numbers of
protein subunits called CAPSOMERES
• The most complex capsids are found in
viruses that infect bacteria –
BACTERIOPHAGES (T1-T7). They
have a protein tail piece with tail fibers
that attach to the bacterium
• Functions that may be fulfilled by the capsid protein are to:
– Protect viral nucleic acid
– Interact specifically with the viral nucleic acid for
packaging
– Interact with vector for specific transmission
– Interact with host receptors for entry to cell
– Allow for release of nucleic acid upon entry into new cell
– Assist in processes of viral and/or host gene regulation
• Capsid proteins are compactly folded proteins which:

– Fold only one way, and robustly

– Vary in size, generally 50-350 aa residues

– Have identifiable domains

– Can be described topologically; similar topological features do not imply

evolutionary relationships

• Capsid is held together by non-covalent, reversible bonds: hydrophobic,

salt, hydrogen bonds

• Nucleocapsid : viral nucleic acid enclosed by a capsid protein coat

 2. Genetic material:
• Genetic material is located inside
the capsid Can be DNA or RNA
 3.Spikes:

• Located on capsid

• Helps viruses attach to cells

• Not present on all viruses
 Basic Nucleocapsid Structures:
• Viruses can assume a range of shapes, some quite complex,
given the dimensions of virus structure and the constraints of
the capsomer’s structural parameters, a very large number
assume any one of regular shapes.
 Helical

 Icosahedral

 Complex
 Helical

• In which the capsomers

associate with helical
nucleic acid as a
nucleoprotein – these can
either be stiff or flexible
depending upon the
properties of the capsid’s
proteins themselves.
• Tobacco mosaic virus
Ebola virus and Rabies
virus are typical, well-
studied examples
TMV rod is 18 nanometers (nm) X 300 nm
• Each particle contains only a single molecule of
RNA (6395 nucleotide residues) and 2130
copies of the coat protein subunit (158 amino
acid residues; 17.3 kilodaltons)
– 3 nt/subunit
– 16.33 subunits/turn
– 49 subunits/3 turns
• TMV protein subunits + nucleic acid will self-
assemble in vitro in an energy-independent
fashion
• Self-assembly also occurs in the absence of
RNA
Coat protein RNA

TMV
 Icosahedral Symmetry
• 12 vertices

• 20 faces
(equilateral triangles)

• 5-3-2 symmetry axes

• 60 identical* subunits
in identical environments
can form icosahedral shell
* asymmetric
 Icosahedral
 In which the capsomers form a regular solid
structure enfolding the viral genome.
 Viruses employ the icoshaderal shape because it
is the most efficient way to enclose a space
 A few genes, sometimes only one, can code for
protein that self assemble to form the capsid
 In this way a small number of linear genes can
specify a large three dimensional- structure
 The capsid are constructed from ring or knob
shaped units called capsomers, each usually
made of five or six protomers
 TBSV icosahedron is 35.4
Icosahedral symmetry nm in diameter

• Tomato bushy stunt

virus is typical, well-
studied example
• Each particle contains
only a single molecule of
RNA (4800 nt) and 180 T= 3 Lattice
copies of the coat protein
C
subunit (387 aa; 41 kd)
• Viruses similar to TBSV
will self-assemble in vitro
from protein subunits + N
nucleic acid in an energy-
independent fashion Protein Subunits Capsomeres
 Complex
• Some viruses possess a capsid that is neither purely helical nor purely icosahedral

• and that may possess extra structures such as protein tails or a complex outer wall

• Enterobacteria phage T4 have complex structure consisting of an icosahedral

head bound to a helical tail, which may have a hexagonal base plate with
protruding protein tail fibres
• Mimivirus is the largest known virus, with a capsid diameter of 400 nm
• It was isolated from amoebae growing in England.
• The mimivirus genome is 1.2 Mb (1,181,404 base pairs). It is
a double-stranded DNA virus.
• Two inverted repeats of 900 base pairs at the ends (thus it may
circularize)
• 72% AT content (~28% GC content)
• 1262 putative open-reading frames (ORFs) of length >100
amino acids. 911 of these are predicted to be protein-coding
genes
• Unique features include genes predicted to encode proteins
that function in protein translation. The inability to perform
protein synthesis has been considered a prime feature of
viruses, in contrast to most life forms.
 Enveloped viruses
• In an enveloped virus, the capsid is covered by an envelope

– The envelope is usually made of some combination of lipids, proteins,

and carbohydrates

– Some envelopes contains spikes that allow them to attach to the host
Enveloped viruses
• Above capsid a protective coat of lipid
bilayer on some viruses
• Made from host cell membrane
(plasma,ER or Golgi)
• The influenza virus and HIV use this
strategy.
• Most enveloped viruses are dependent on
the envelope for their infectivity
Properties of enveloped viruses

From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. Box 6-5.
 Non enveloped viruses
• The nucleic acid of a virus is surrounded by a capsid.

• Each capsid is composed of protein subunits called capsomeres

• But the lipid bilayer is absent due to which it is called as non
enveloped virus e.g. Human Papillomavirus
Properties of non enveloped viruses

From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Box 6-4.
Structure of Animal Viruses
Techniques used in study of virus
structure:
– Transmission electron microscopy (EM)

– Cryo EM – one of the most powerful methods currently

available
– X-Ray diffraction

– Neutron scattering

– Primary sequence analysis

– Protease and foot printing

– Site-directed mutagenesis
 CLASSIFICATION AND
NOMENCLATURE OF VIRUSES
 What is the purpose of
classification?
 To make order

• Effective organization schemes facilitate and focus study

 To be able to communicate with each other

• The better the classification system, the fewer explanatory

words are needed
 To assemble like members with each other

• It is important to identify the qualities that are considered in

a classification scheme
 How are viruses named?
• Based on:
- the disease they cause
poliovirus, rabies virus
- the type of disease
murine leukemia virus
- geographic locations
Sendai virus, Coxsackie virus
- their discovers
Epstein-Barr virus
- how they were originally thought to be contracted
dengue virus (“evil spirit”), influenza virus (the “influence” of bad air)
- combinations of the above
Rous Sarcoma virus
 A good strategy
for remembering the basics of virus classification is to keep
track of the following:
1. What kind of genome is in the capsid:
a) Is it DNA or RNA?
b) Is it single stranded or double stranded?
c) Is the genome circular or linear, composed of a single or
segmented?
2 How is the protein arranged around the nucleic acid;
a) what are the symmetry and
b) dimensions of the viral capsid?
3. Are there other components of the virion?
a) Is there an envelope?
b) Are there enzymes in the virion required for initiation of
infection or maturation of the virion?
 Classification systems
 Two classification systems exist:
 ICTV classification system
 The Baltimore Classification System
ICTV classification system:
 International Commetie on Taxonomy of Virus describes
rules for the clssification of viruses in early 1990s.
 According to them viral classification starts at the level of
order and follows as thus, with the taxon suffixes given in
italics:
 ICTV classification of virus
-Order (-virales)
-Family (-viridae)
-Subfamily (-virinae)
-Genus (-virus)
Species
 Examples:
1. For example, the Ebola virus from Kikwit is classified as:
Order Mononegavirales
Family Filoviridae
Genus Filovirus
Species: Ebola virus Zaire

2. Family Herpesviridae
Subfamily Betaherpesvirinae
|Genus Muromegalovirus
Type species Murine herpesvirus 1
 The Baltimore classification
system
 In 1971, David Baltimore suggested a scheme for virus
classification based on the way in which a virus produces
messenger RNA (mRNA) during infection.
 The logic of this consideration is that in order to replicate, all
viruses must express mRNA for translation into protein, but
how they do this is determined by the type of genome utilized
by the virus.
 In this system, viruses with RNA genomes whose genome is
the same sense as mRNA are called positive (+)-sense RNA
viruses, while viruses whose genome is the opposite
(complementary) sense of mRNA are called negative
(-)-sense RNA viruses
The Baltimore classification system
Based on genetic contents and replication strategies of viruses.
According to the Baltimore classification, viruses are divided
into the following seven classes:
1. dsDNA viruses
2. ssDNA viruses
3. dsRNA viruses
4. (+) sense ssRNA viruses (codes
directly for protein)
5. (-) sense ssRNA viruses
6. RNA reverse transcribing viruses
7. DNA reverse transcribing viruses

where "ds" represents "double strand" and

"ss" denotes "single strand".
The Baltimore classification system
The Baltimore classification system
Classification of Plant viruses
Classification of human viruses
Insert Table 24.1
DNA viruses

52
 Classification of Human Viruses
"Group" Family Genome Genome size (kb) Capsid Envelope
dsDNA
Poxviridae dsDNA, linear 130 to 375 Ovoid Yes
Herpesviridae dsDNA, linear 125 to 240 Icosahedral Yes
Adenoviridae dsDNA, linear 26 to 45 Icosahedral No
Polyomaviridae dsDNA, circular 5 Icosahedral No
Papillomaviridae dsDNA, circular 7 to 8 Icosahedral No
ssDNA
Anellovirus ssDNA circular 3 to 4 Isometric No
Parvoviradae ssDNA, linear, (- or +/-) 5 Icosahedral No
Retro
Hepadnaviridae dsDNA (partial), circular 3 to 4 Icosahedral Yes
Retroviridae ssRNA (+), diploid 7 to 13 Spherical, rod or cone shaped Yes
dsRNA
Reoviridae dsRNA, segmented 19 to 32 Icosahedral No
ssRNA (-)
Rhabdoviridae ssRNA (-) 11 to 15 Helical Yes
Filoviridae ssRNA (-) 19 Helical Yes
Paramyxoviridae ssRNA (-) 10 to 15 Helical Yes
Orthomyxoviridae ssRNA (-), segmented 10 to 13.6 Helical Yes
Bunyaviridae ssRNA (-, ambi), segmented 11 to 19 Helical Yes
Arenaviridae ssRNA (-, ambi), segmented 11 Circular, nucleosomal Yes
Deltavirus ssRNA (-) circular 2 Spherical Yes
ssRNA (+)
Picornaviridae ssRNA (+) 7 to 9 Icosahedral No
Calciviridae ssRNA (+) 7 to 8 Icosahedral No
Hepevirus ssRNA (+) 7 Icosahedral No
Astroviridae ssRNA (+) 6 to 7 Isometric No
Coronaviridae ssRNA (+) 28 to 31 Helical Yes
Flaviviridae ssRNA (+) 10 to 12 Spherical Yes
Togaviridae ssRNA (+) 11 to 12 Icosahedral Yes
Major diseases caused by human viruses
"Group" Family Human pathogens (disease)
dsDNA
Poxviridae Variola (smallpox); Orf (pustular dermatitis); Molluscum contagiosum (pustular dermatitis)
Herpesviridae Herpes simplex 1,2 (oral, genital herpes); Varicella-zoster (chickenpox); Epstein-Barr (mononucleosis);
Cytomegalovirus (neonatal abnormalities); HHV6 (roseola); HHV8 (Kaposi's sarcoma)
Adenoviridae Adenovirus (respiratory infection, conjunctivitis)
Polyomaviridae Polyomavirus (benign kidney infection, respiratory disease, leukoencephalopathy)
Papillomaviridae Papillomavirus (warts, genital carcinoma)
ssDNA
Anellovirus Unknown
Parvoviradae B-19 (fifth disease, fetal death)
Retro
Hepadnaviridae Hepatitis B ("serum" hepatitis)
Retroviridae HIV (aids); HTLV (leukemia)
dsRNA
Reoviridae Rotavirus (infantile gastroenteritis)
ssRNA (-)
Rhabdoviridae Rabies virus (rabies)
Filoviridae Ebola virus (ebola)
Paramyxoviridae Parainfluenza virus (respiratory infection); Mumps virus (mumps);
Respiratory syncytial virus (respiratory infection); Measles virus (measles)
Orthomyxoviridae Influenza virus (influenza)
Bunyaviridae Hantaan virus (hemorrhagic fever with renal syndrome)
Arenaviridae Lassa fever virus (hemorrhagic fever)
Deltavirus Hepatitis D (fulminant acute hepatitis)
ssRNA (+)
Picornaviridae Poliovirus (polio), rhinovirus (URI), Hepatitis A ("infectious" hepatitis)
Calciviridae Norwalk (gastroenteritis)
Hepevirus Hepatitis E (acute hepatitis)
Astroviridae Astrovirus (gastroenteritis)
Coronaviridae Coronavirus (respiratory infection)
Flaviviridae Yellow fever virus (yellow fever); Hepatitis C (hepatitis)
Togaviridae Eastern Equine encephalitis virus (encephalitis); Rubella virus (rubella)
55
 Viral Genome
 Depending on the virus, viral genomes:
 The genomes (sets of genes) maybe
– Double stranded DNA
– Single stranded DNA
– Double stranded RNA
– Single stranded RNA
 They are called either a DNA or RNA virus depending on the
type of nucleotide in the make-up.
 They may be linear or circular
 The smallest have only 4 genes and largest have several
hundred
 DNA VIRUS RNA
GENOMES
Single Stranded + or -

Double Stranded Segmented

Double Stranded Segmented

Circular
DNA viruses

From Principles of
Virology Flint et al
ASM Press
RNA viruses

From Principles of Virology Flint et al ASM Press

 Types of viral genome
1.Double-stranded DNA

2. Single-stranded (+)sense DNA

3.Double-stranded RNA

4.Single-stranded (+)sense RNA

5. Single-stranded (-)sense RNA

6.Single-stranded (+)sense RNA with DNA intermediate in life-cycle

7.Partial double-stranded (gapped) DNA with RNA intermediate

 1. dsDNA Viruses
 Examples of dsDNA viruses that infect humans

– Adenoviruses , Herpesviruses, Papillomaviruses,

Poxiviruses, T4 bacteriophage
 Among the largest known viruses

 Genome size varies from 5 to 1180 Kb

 Unfragmented genomes

 Both linear and circular

 Large genome size attributed to stability of dsDNA

 Low error rate during replication

 Some replicate in the nucleus e.g adenoviruses using cellular

proteins. Poxviruses replicate in the cytoplasm
 No dsDNA virus is known to infect plants

 Phages are dsDNA viruses (95%)

 2. Single-stranded (+)sense DNA

 ssDNA Viruses have the following characteristics

– Small genome, 2-7 Kb
• Possibly due to unstable nature of ssDNA compared to
dsDNA
– Circular genomes with the exception of Parvoviridae
(hairpin)
– No envelope
– Predominantly icosahedral capsids
 Examples of dsDNA viruses
phage M13, chicken anaemia virus, maize streak virus
 Replication occurs in the nucleus, involving the formation of a
(-)sense strand, which serves as a template for (+)strand RNA
and DNA synthesis
 3.Double-stranded RNA
 They utilize RNA dependent polymerase

 Icosahedral capsids

 Capsids stays intact inside cell.

 Transcription occurs via viral RNA polymerases

 Examples : Reoviruses, Rotavirues

 Reoviruses (dsRNA) are capable of infecting multiple species

(plants, vertebrates, fungi). Not a common phenomenon.
 Rhabhoviridae infect multiple species as well

 The fact that they carry their own RNA

replication/transcription proteins
 These viruses have segmented genomes. Each genome
segment is transcribed separately to produce monocistronic
mRNAs.
 4.Single-stranded (+)sense RNA
 Very common of plant viruses to be + ssRNA

 Examples : Hepatitis A and C, Small RNA phages, common cold

viruses, SARS
 Only one phage family is + ssRNA

 RNA viruses have linear genomes

 Similar to ssDNA viruses they are susceptible to nucleases and

divalant cation degradation
 Coronavirus has the largest genome of + ssRNA virus (16-30 Kb)
a) Polycistronic mRNA e.g. Picornaviruses; Hepatitis A. Genome RNA =
mRNA.
 Means naked RNA is infectious, no virion particle associated
polymerase.
 Translation results in the formation of a polyprotein product, which is
subsequently cleaved to form the mature proteins.

b) Complex Transcription e.g. Togaviruses.

 Two or more rounds of translation are necessary to produce the
genomic RNA.
 5. Single-stranded (-)sense RNA

 This group includes some of the deadliest viruses

– Ebola, rabies, influenza, measles

 Only helical nucleocapsids

 Must have a virion particle, containing RNA directed RNA

polymerase
 Nucleocapsid seems to provide stability for RNA dependent
RNA polymerase to generate + ssRNA
 + ssRNA=mRNA
a) Segmented e.g. Orthomyxoviruses.
• First step in replication is transcription of the (-)sense RNA
genome by the virion RNA-dependent RNA polymerase to
produce monocistronic mRNAs, which also serve as the
template for genome replication.

b) Non-segmented e.g. Rhabdoviruses.

• Replication occurs as above and monocistronic mRNAs are
produced
 6.Single-stranded (+)sense RNA
with DNA intermediate in life-
cycle
 3 families belong to this group
– Retroviridae, Ex. HIV
– Hepadnaviridae, Ex. Hep B
– Caulimoviridae, Ex. Cauliflower Mosaic Virus
 These families utilize enzyme that uses an RNA template to
make DNA template
 Reverse transcriptase is packaged in capsid
– Similar to + ssRNA and – ssRNA that package the RNA
dependent polymerase
 Retroviruses package 2 copies of their RNA genome in the
capsid
 7.Partial double-stranded (gapped)
DNA with RNA intermediate
 Example: Hepatitis B

 This group of viruses also relies on reverse transcription, but

unlike the Retroviruses, this occurs inside the virus particle on
maturation.
 On infection of a new cell, the first event to occur is repair of
the gapped genome, followed by transcription.
VIROSPHERE