Structures of

a Virus
A Tour to the natures deadliest weapon.

Recall:
Whats the difference
between virus and
virion?
Virion are complete viral
particle that consist of a
genome with a protein
coat or with a external
envelope at time
Extracellular infective
form of a virus

VIRION
Gene delivery system containing
the genome
So what does a virion function for?
Protects the genome
Protein aids in entry to host
Replicate the genome packaged
in a capsid

What are the main

structures of a virion?
1. Genome
2. Capsid
3. Lipid envelope (may be present)
4. Protein occlusion bodies (for
protection)

1. Viral genome
Virion contains a
genome
May consist of one or
more nucleic acid
Can be RNA or DNA
During isolation how can
one identify if the virion
contains DNA or RNA?
Testing for
susceptibility on
Ribonuclease.

Classification of virion based on

nucleic acid
1.ds DNA encode
genes same way as
plants, animals,
bacteria
2.ss DNA circovirus
3.ds RNA typical for
fungal viruses
4.ss RNA most
plant viruses

Virion genome can

also be classified as:
1. Linear
with free 5 and
3 ends,
2. Circular
covalently
closed
Virion genome also
contains:

+
What is meant by
these signs on the
genome?

 most of the nucleic acid strands are labelled (+)

or ().
RNA+ or RNA labelling is relative to the virus mRNA, always
designated (+)
nucleic acid strand that has the same sequence
as mRNA is labelled (+)
and a nucleic acid strand that has the sequence
complementary to the mRNA is labelled ().

Positive-sense

Positive-sense (5' to 3') viral RNA signifies that a particular viral RNA sequence may
be directly translated into the desired viral proteins.

Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered
viral mRNA, and can be immediately translated by the host cell.

Unlike negative-sense RNA, positive-senseRNAisofthesamesenseasmRNA.

Some viruses (e.g., Coronaviridae) have positive-sense genomes that can act as
mRNA and be used directly to synthesize proteins without the help of a
complementary RNA intermediate.

Because of this, these viruses do not need to have an RNA polymerase packaged into
the virion.

Negative-sense

Negative-sense (3' to 5') viral RNA is complementary to the viral mRNA and thus from
it a positive-sense RNA must be produced by an RNA-dependent RNA
polymerase prior to translation.

Negative-sense RNA (like DNA) has a nucleotide sequence complementary to

the mRNA that it encodes.

Like DNA, this RNA cannot be translated into protein directly. Instead, it must first be
transcribed into a positive-sense RNA that acts as an mRNA.

Some viruses (Influenza, for example) have negative-sense genomes and so must
carry an RNA polymerase inside the virion.

Buttake a look at:

DNA in hepadnavirus virions
RNA in inuenza virions
Some linear
molecules may be
in a circular
conformation as a
result of base
pairing between
complementary
sequences at their
ends

Virion span ranges of

genome size
Porcine circovirus
(ssDNA)
and hepatitis delta
virus (ssRNA) each
have a genome of
about 1.7 kilobases
(kb),
dsDNA genomes
comprised of over
1000 kilobase pairs
(kbp).
The maximum size of a
virus genome is subject
to constraints, which

1.2. Genome
size

As the constraints are

less severe for dsDNA
all of the large virus
genomes are composed
of dsDNA.
The largest RNA
genomes known are
those of some
coronaviruses, (33 kb of
ssRNA)
Largest virus genomes
the mimivirus, larger
than mycoplasmas.

1.3 Secondary and Tertiary Structures

Information carried by the viral genome:
1. Encode viral proteins
2. Encode untranslated RNA
3. Signals control of gene expression
SIGNALS are found on:
d.s. within the nucleotide
s.s. contained within structures formed by
intramolecular base pairing.

S.S. GENOME
s.s. DNA
Base pair through G-C
A- T hydrogen bonding
s.S RNA
weaker GU bonds may form
in addition to GC and AU
base pairing.
Intramolecular base pairing
results in regions of secondary
structure with stem- loops and
bulges

ssRNAS

Formation of
pseudoknots may form
Functions for genome
replication

Internal ribosome entry site

Tertiary
structure

Regions of secondary structure in singlestranded nucleic acids are folded with

specific shapes
depicts the 5 end of poliovirus RNA
there is an internal ribosome entry site to
which cell proteins bind to initiate

Some pseudoknots have

enzyme activity, while others
play a role in ribosomal
frameshifting.

What is ribosomal frameshifting?

a second ORF in an mRNA involves ribosomal frameshifting

a ribosome shifts into a different reading frame towards the end of
ORF 1.

It therefore does not recognize the ORF 1 stop codon,

but continues along the mRNA, reading ORF 2

to produce an elongated version of the ORF 1 protein

 Frameshifting occurs when the ribosome moving along the

RNA
encounters a frameshift signal (a specific sequence) followed
by a secondary structure, usually a pseudoknot.

1.4. Modification at the end

genomes of some DNA viruses and many RNA viruses are modified at
one or both ends

Some genomes have a covalently linked protein at the 5 end.

a vestige of a primer
used for initiation of genome synthesis

RNA viral genome with

one or both ends
modified
The 5end may be
linked to a protein or a
methylated nucleotide
cap
The 3 end may be
polyadenylated or it
may be folded like a
transfer RNA

Some genome RNAs have one or both of the modifications

occur in eukaryotic messenger RNAs (mRNAs):
a. a methylated nucleotide cap at the 5 end
b. a sequence of adenosine residues (a polyadenylate tail; poly(A)
tail) at the 3 end)

The genomes of many

RNA viruses function as
mRNAs (during
infection)
cap and a poly(A) tail
on a genome RNA may
indicate that the
molecule is ready to
function as mRNA,
but neither structure is
essential for translation.
All the ssRNAs function
as mRNAs,
but not all have a cap
and a poly(A) tail.

In the case of plant viruses

genomes of some ssRNA plant viruses
are base paired
and folded near their 3 ends
to form structures similar to transfer
RNA.
structures contain sequences that
promote the initiation of RNA
synthesis.

1.5 proteins non covalently

associated with virus genomes
nucleic acids packaged in
virions have proteins bound
to them non-covalently
encoded in two or more
nucleic acid molecules
segmented genomes are
much more common
amongst RNA viruses than
DNA viruses. (inuenza
virus, ssRNA)
package the segments in
one virion,
Most dsRNA viruses, such
as members of the family
Reoviridae have segmented
genomes.

possession of a segmented genome provides

a virus with the possibility of new gene
combinations
and hence a potential for more rapid evolution
viruses with the segments packaged in separate
virions
A new cell becomes infected only if all genome
segments enter the cell, which means that at least
one of each of the virion categories must infect.

1.5 Repeated sequences

These sequences include:
promoters,
enhancers,
origins of replication
and other elements involved in
the control of events in virus
replication.

 linear virus genomes

have repeat sequences at
the ends (termini),

in which case the

sequences are known as
terminal repeats

If the repeats are in the

same orientation they are
known as direct terminal
repeats (DTRs),
whereas if they are in the
opposite orientation they
are known as inverted
terminal repeats (ITRs).

 the sequences
referred to as ITRs in
single-stranded
nucleic acids are
NOT REPEATS
But until the second
strand is synthesized
during replication.
In the single-stranded
molecules the ITRs
are, in fact, repeats of
the complementary
sequences
see ssDNA and ssRNA
()

2. Viral Protein
As the size of the genome increases, so the
number of protein species tends to increase
FACT!
tobacco mosaic virus contains only one protein
species
parvoviruses contain two to four protein species.
herpes simplex virus 1 contains 39 protein species
algal virus Paramecium bursaria Chlorella virus 1
contain 100 protein species

Proteins that are components of virions

are known as structural proteins
Functions:
protection of the virus genome
attachment of the virion to a host cell (for many
viruses)
fusion of the virion envelope to a cell membrane (for
enveloped viruses).
Other ROLES:
enzymes, e.g. protease, reverse transcriptase
transcription factors
primers for nucleic acid replication
interference with the immune response of the host.

Can we classify virus based on protein?

 In a virion the virus genome is enclosed in a

protein coat, known as a capsid.
the genome and the capsid constitute the
virion,
while for other viruses there are additional
components.
may be an envelope at the surface of the
virion,

in which case there may be:

a.protein between the envelope and
the capsid,
b.an internal lipid membrane.

Virus genomes removed from

CAPSIDS

their capsids are more susceptible

to inactivation,
major function of the capsid:
the protection of the genome

Second major function:

recognize and attach to a host cell in
which the virus can be replicated
capsid is the protein shell of a virus.
consists of several oligomeric structural

subunits made of protein called protomers.

Observable 3-dimensional morphological
subunits, which may or may not correspond
to individual proteins, are
called capsomeres.
Capsid encloses the genetic material of the
virus.

Protomer:
aPROTOMERis the structural unit of
anoligomeric protein.
A PROTOMER can be aprotein subunitor several
different subunits, that assemble in a defined
stoichiometryto form anoligomer.
protomer is the smallest subset of different
subunits that form the oligomer.
The PROTOMER usually arrange incyclic
symmetryto form closedpoint
groupsymmetries.
Protomers are the main subunit in a viralcapsid.

For many viruses the capsid and the

genome that it encloses constitute the
virion.
For other viruses a lipid envelope
and sometimes another layer of protein,
surrounds this structure, which is
referred to as a nucleocapsid.

 Capsids are
constructed from
many molecules of
one or a few
species of protein.
The individual
protein molecules
are asymmetrical,
but they are
organized to form
symmetrical
structures.
Some examples of
symmetrical
structures are

Symmetrical
including a capsid,
has the same appearance when it is
rotated through one or more angles,
or when it is seen as a mirror
image.
capsid symmetry is either
helical or icosahedral.

Capsids with
symmetrical symmetry
The capsids of many
ssRNA viruses have helical
symmetry;
the RNA is coiled in the
form of a helix,
many copies of the same
protein species are
arranged around the coil
(Figure 3.9(a), (b)).

 forms an elongated
structure,
may be a rigid rod if
strong bonds are present
between the protein
molecules in successive
turns of the helix,
or a exible rod if these
bonds are weak.

The length of the capsid is

determined by the length of the
nucleic acid

For many ssRNA

viruses
(such as measles and
inuenza viruses)
the helical nucleic acid
coated with protein
forms a nucleocapsid,
which is inside an
envelope.
The nucleocapsid may
be coiled or folded to
form a compact
structure.

The virions of some plant

viruses that have helical
symmetry (e.g. tobacco
mosaic virus)
are hollow tubes;
allows the entry of
negative stain,
making the center of the
virion appear dark in
electron micrographs.
The rod-shaped tobacco
rattle virus has a
segmented genome with
two RNAs of different
sizes packaged in
separate virions
resulting in two lengths

The virion of a
few DNA
viruses, such
as the
filamentous
phages also
have helical
symmetry

Capsids with icosahedral symmetry

What is an icosahedron?
An icosahedron is an object
with:
20 faces, each an
equilateral triangle;
12 vertices, each formed
where the vertices of five
triangles meet;
30 edges, at each of which
the sides of two triangles

An
icosahedron
has five-,
threeand two-fold
axes of
rotational
symmetry

Capsids with icosahedral symmetry

consist of :
a shell built from protein molecules
appear to have been arranged on
scaffolding in the form of an
icosahedron.
have less contact with the virus
genome than the capsid proteins of
viruses with helical symmetry.

To construct an
icosahedron from
identical protein
molecules:
the minimum number
of molecules required is
three per triangular
face,
giving a total of 60 for
the icosahedron (Figure
3.11(a)).
The capsid of satellite
tobacco mosaic virus is
constructed in this way
(Figure 3.11(b)).

The capsids of many

icosahedral viruses are:
composed of more than
one protein species.
That of cowpea mosaic
virus is composed of two
proteins (Figure 3.12):
one is present as
pentamers at the
vertices of the
icosahedron (125 = 60
copies) and the other is
present as hexamers on
the faces.
hexamer is composed of
three copies of a protein
with two domains.
The arrangement is
similar to that of the
panels on the surface of

 some capsids
actually have the shape
of an icosahedron,
such as that of
Paramecium bursaria
Chlorella virus 1,
which is 165 nm
across when
measured along the
two- and three-fold
axes and 190 nm
across when
measured along the
five- fold axes.
Capsids that have an
icosahedral shape have

 An icosahedral shape is not

an inevitable outcome of
icosahedral symmetry;
the football is constructed
in the form of icosahedral
symmetry,
but the structure is
spherical.
Many small viruses that
have capsids with
icosahedral symmetry
appear to be spherical, or
almost spherical,
their virions are often
described as isometric,
such as those of
densoviruses and foot and
mouth disease virus (Figure
3.13).

 Some capsids with icosahedral

symmetry are elongated.
capsids of geminiviruses (plant
viruses) are formed from two
incomplete icosahedra. (above)

Another plant virus, alfalfa

mosaic virus, has four sizes of
virion; all are 19 nm diameter,

but three are elongated as a

result of insertions of a protein
lattice between a half
icosahedral structure at each
end of the capsid. (beside)

Prolate
This is an icosahedron
elongated along the
fivefold axis
common arrangement
to heads of
bacteriophages
Such a structure is
composed of a cylinder
with a cap at either end.
The cylinder is
composed of 10
triangles.

capsomeres
Thecapsomereis a subunit of
thecapsid, an outer covering
ofprotein that protects the
genetic material of avirus.
Capsomeres self-assemble to
form the capsid.
In this diagram of anAdenovirus,
the capsid molecules are clearly
visible.
Subunits
calledprotomersaggregate to
form capsomeres.
Various arrangements of
capsomeres are: 1) Icosahedral,
2) Helical, and 3) Complex.

 The capsids of papillomaviruses

are constructed from 72
capsomeres,
which are all identical,

but the capsids of some viruses

are constructed from two types
of capsomere:

a. pentons, which are found at the

vertices of the icosahedron,
b. hexons, which make up the
remainder of the capsid. In these
viruses there are always 12
pentons (one at each vertex),
but the number of hexons varies;
for example, the capsids of
herpesviruses and adenoviruses
contain 150 and 240 hexons,
respectively.

Capsid vertices
icosahedral viruses have a
structure such as a knob,
projection or fibre at each of
the 12 vertices of the capsid.
For example, the virions of
some phages (e.g. G4; Figure
3.13)
have projections, while the
adenovirus virion has a fibre,
(larger image)
with a knob attached, at each
of the 12 pentons
structures at the capsid
vertices are composed of
distinct proteins that are
involved in attachment of the

Tailed bacteriophage
The majority of the
known phages are
constructed in the form
of a tail attached to a
head,
contains the virus
genome.
All of these phages have
dsDNA genomes.
The head has icosahedral
symmetry and may be
isometric as in phage
lambda (),
or elongated as in phage
T4.
The tail, which is
attached to one of the

 may contain specialized

structures such as fibres
and/or a baseplate.

Some of the tailed phages

have been objects of intensive
study and a lot of the detail of
their structures has been
uncovered.
One such phage is T7

Inside the head of phage T7 is

a cylindrical structure (the
internal core) around which
the DNA is wound.
The connector has a wider
region inserted into one of the
vertices of the head
and a narrower region to
which the tail is attached.

The tail is very short and

Conical and rod-shaped capsids

HIV-1 and baculoviruses have
capsids that are conical and rod
shaped, respectively
Inside each capsid is a copy of
the virus genome coated in a
highly basic protein.
Both of these viruses have
enveloped virions

VIRION MEMBRANES
Many viruses have a lipid
membrane component.
In most of these viruses the
membrane is at the virion
surface
and is associated with one or
more species of virus protein.
This lipidprotein structure is
known as an envelope
and it encloses the
nucleocapsid (nucleic acid plus
capsid).
The virions of most enveloped
viruses, such as herpesviruses,
are spherical or roughly
spherical, but other shapes
exist (Figure 3.19).

Some viruses have a

membrane located not at the
virion surface, but within the
capsid.

Envelope virion
Facts on viral envelopes:
Manyviruses(e.g. inuenza and many animal
viruses) haveviral envelopescovering their
protective proteincapsids.
The envelopes typically are derived from
portions of the hostcell
membranes(phospholipidsand proteins), but
include some viral glycoproteins.
Functionally, viral envelopes are essential to
entry intohostcells.
They may help viruses avoid the hostimmune
system.
Glycoproteins on the surface of the envelope
serve to identify and bind toreceptor siteson the
host's membrane.

 Associated with the

membranes of an enveloped
virus are one or more species
of protein.
Most of these proteins are
integral membrane proteins
and most are O- and/or Nglycosylated.
Many of the glycoproteins in
virion envelopes are present
as multimers.
The envelope of inuenza A
virus for example, contains
two glycoprotein species: a
haemagglutinin present as
trimers
and a neuraminidase present
as tetramers.

 Some envelope proteins

span the membrane
only once
but some, such as those
of hepatitis B virus span
the membrane several
times.
The polypeptide chain
is highly hydrophobic at
each membrane anchor.

 Some surface glycoproteins of

enveloped viruses perform the
function of fusing the virion
membrane to a cell membrane
during the infection process
These fusion proteins have an
additional hydrophobic region
plays a major role in the fusion
process.
Many enveloped viruses, including
inuenza viruses and retroviruses
have a layer of protein between
the envelope and the
nucleocapsid.
This protein is often called a
matrix protein.
In some viruses, however, such as
yellow fever virus, such layer
and the nucleocapsid interacts
directly with the internal tails of
the integral membrane protein
molecules.

Membrane lipids
Most virion membranes are
derived from host cell
membranes that undergo
modification before
incorporation into virions.
For example, the HIV-1
envelope is derived from
the plasma membrane of
the host cell
but the virus envelope
contains more cholesterol
and sphingomyelin,
and less
phosphatidylcholine and

Occlusion bodies
Some viruses provide added protection to the virions while outside their hosts by
occluding them in protein crystals.
These occlusion bodies, as they are known, are produced by many of the viruses
that infect invertebrates, including most baculoviruses.
There are two major types of occlusion body in which baculoviruses embed their
rod-shaped virions;
the granuloviruses form small granular occlusion bodies, generally with a single
virion in each
the nucleopolyhedroviruses form large occlusion bodies with many virions in each

Cell molecules
The incorporation of cell lipids into virions has already
been discussed.
Other cell molecules that become incorporated into
virions include the following.
Transfer RNA molecules. These are present in the
virions of retroviruses.
Proteins. When a virion is assembled some cell
protein may be incorporated. There are reports of HIV-1
incorporating several cell proteins, including cyclophilin
A in association with the capsid and human leukocyte
antigens in the envelope.
Polyamines. Spermidine and other polyamines have
been reported in a variety of viruses.
Cations, such as Na+,K +, Zn 2+ and Mg2+ have also
been reported as components of virions. One likely role

To be passed next week:

Does the difference on viral genome affects
infectivity or rate of infectivity of viruses?
1 whole paper, hand written
outline important points
Explain by citing helpful literatures, and
sample virus or disease.