Download Basic virology

Basic virology
Chapter 28
Structure
Prepared by :
Ibtihal El-agha
VIRAL NUCLEIC ACIDS :
The viral nucleic acid (genome) is located
internally.
 It can be either single- or double-stranded
DNA or single- or double-stranded RNA.
The nucleic acid can be either linear or
circular.
The DNA is always a single
molecule.
The RNA can exist either as a single
molecule or in several pieces.
For example, both influenza virus
and rotavirus have a segmented RNA
genome.
influenza virus
 Almost all viruses contain only a
single copy of their genome; ie, they are
haploid.
 The exception is the retrovirus
family, whose members have two
copies of their RNA genome; ie, they are
diploid.
retrovirus
SIZE & SHAPE :
 Viruses range from 20 to 300 nm in
diameter.
 This corresponds roughly to a range of sizes
from that of the largest protein to that of the
smallest cell.
 Spheres, rods, bullets, or bricks.
 They are complex structures of precise
geometric symmetry.
 The shape of virus particles is
determined by the arrangement of the
repeating subunits that form the protein coat
(capsid) of the virus.
VIRAL CAPSID & SYMMETRY :
 The nucleic acid is surrounded by a protein coat
called a capsid, made up of subunits called
capsomers.
 Each capsomer, consisting of one or several
proteins .
 The structure composed of the nucleic acid genome
and the capsid proteins is called the nucleocapsid.
arrangement of capsomers gives the virus
structure its geometric symmetry.

 Viral nucleocapsids have two forms of symmetry:
(1) icosahedral, in which the capsomers are
arranged in 20 triangles that form a symmetric figure
(an icosahedron) with the approximate outline of a
sphere.
 (2) helical, in which the capsomers are arranged
in a hollow coil that appears rod- shaped. The helix
can be either rigid or flexible.
 All human viruses that have a helical
nucleocapsid are enclosed by an outer
membrane called an envelope.
 There are no naked helical viruses.
 Viruses that have an icosahedral
nudeocapsid can be either enveloped or
naked.
The advantage of building the virus particle
from identical protein subunits is 2-fold:
(1)it reduces the need for genetic information.
(2)it promotes self- assembly; ie, no enzyme or
energy is required. In fact, functional virus
particles have been assembled in the test tube
by combining the purified nucleic acid with
the purified proteins in the absence of cells,
energy source, and enzymes.
VIRAL ENVELOPE :
 The envelope is a lipoprotein membrane composed of :
1) lipid derived from the host cell membrane .
2) protein that is virus-specific.
There are frequently glycoproteins in the form of
spike- like projections on the surface, which attach to
host cell receptors during the entry of the virus into the
cell.
The matrix protein, mediates the interaction
between the capsid proteins and the envelope.
The viral envelope is acquired as the virus
exits from the the cell in a process called
"budding" .
The envelope of most viruses is derived
from the cell's outer membrane.
Exception of herpesviruses that derive
their envelope from the cell's nuclear
membrane.
 The presence of an envelope confers instability on
the virus.
Enveloped viruses are more sensitive to heat, drying,
detergents, and lipid solvents such as alcohol and
ether than are nonenveloped (nucleocapsid) viruses.
virtually all viruses that are transmitted by the fecaloral route (those that have to survive in the environment)
do not have an envelope.
 These include viruses such as hepatitis A virus,
poliovirus, coxsackievirus, echovirus, Norwalk virus,
and rotavirus.
 In contrast, enveloped viruses are most often
transmitted by direct contact, such as by blood or by
sexual transmission.
 Examples of these include human immunodeficiency
virus, herpes simplex virus type 2, and hepatitis B and C
viruses.
 Other enveloped viruses are transmitted directly by
insect bite, eg, yellow fever virus and West Nile virus, or
by animal bite, eg, rabies virus.
Many other enveloped viruses are transmitted from
person to person in respiratory aerosol droplets, such
as influenza virus, measles virus, rubella virus,
respiratory syncytial virus, and varicella-zoster virus.
If the droplets do not infect directly, they can dry out
in the environment, and these enveloped viruses are
rapidly inactivated.
Rhinoviruses, which are transmitted by
respiratory droplets, are naked nucleocapsid viruses
and can survive in the environment for significant
periods.
VIRAL PROTEINS :
Viral proteins serve several important
functions:
The outer capsid proteins protect the
genetic material .
mediate the attachment of the virus to
specific receptors on the host cell surface.
This interaction of the viral proteins with
the cell receptor is the major determinant of
species and organ specificity.
Outer viral proteins are also important
antigens.
Induce neutralizing antibody and activate
cytotoxic T cells to kill virus-infected cells.
These outer viral proteins not only induce
antibodies but are also the target of antibodies,
ie, antibodies bind to these viral proteins and
prevent ("neutralize") the virus from entering
the cell and replicating.
 They are also the determinants of type specificity
(often called the serotype).
Some viruses produce antigenic variants of their
surface proteins that allow the viruses to evade our
host defenses.
 For example, poliovirus types 1, 2, and 3 are
distinguished by the antigenicity of their capsid
proteins.
 Antibody against one serotype will not protect
against another serotype.
It is important to know the number of serotypes
of a virus, because vaccines should contain the
prevalent serotypes. There is often little crossprotection between different serotypes.
Viruses that have multiple serotypes, ie, have
antigenic variants, have an enhanced ability to
evade our host defenses .
The internal viral proteins are :
1) Structural: the capsid proteins of the enveloped
viruses.
2) Enzymes : the polymerases that synthesize the
viral mRNA.
The internal viral proteins vary depending on the
virus.
Some viruses have a DNA or RNA polymerase
attached to the genome; others do not.
Some viruses produce proteins that act as "super-
antigens" .
Viruses known to produce superantigens include :
1) Two members of the herpesvirus family, namely,
Epstein- Barr virus and cytomegalovirus.
2) The retrovirus mouse mammary tumor virus.
The current hypothesis offered to explain why these
viruses produce a super- antigen is that activation of
CD4-positive T cells is required for replication of
these viruses to occur.
ATYPICAL VIRUSLIKE AGENTS :
There are four exceptions to the typical virus as described above:
(1)Defective viruses :
 are composed of viral nucleic acid and proteins but
cannot replicate without a "helper" virus, which
provides the missing function.
 usually have a mutation or a deletion of part of their
genetic material.
 During the growth of most human viruses, many
more defective than infectious virus particles are
produced.
 The ratio of defective to infectious particles can
be as high as 100:1.
 Because these defective particles can interfere with
the growth of the infectious particles, it has been
hypothesized that the defective viruses may aid in
recovery from an infection by limiting the ability of
the infectious particles to grow.
(2) Pseudovirions :
 Contain host cell DNA instead of viral DNA within
the capsid.
 They are formed during infection with certain viruses
when the host cell DNA is fragmented and pieces of it
are incorporated within the capsid protein.
 Pseudovirions can infect cells, but they do not
replicate.
(3) Viroids :
 Consist solely of a single molecule of circular
RNA without a protein coat or envelope.
 The RNA is quite small and apparently does not
code for any protein.
 Nevertheless, viroids replicate but the mechanism
is unclear.
 They cause several plant diseases but are not
implicated in any human disease.
(4) Prions :
Prions are infectious particles composed entirely of
protein. They have no DNA or RNA.

 They cause diseases such as Creutzfeldt-Jakob
disease and kuru in humans and mad cow disease and
scrapie in animals.
 These diseases are called transmissible spongiform
encephalopathies. The term spongiform refers to the
sponge-like appearance of the brain seen in these
diseases. The holes of the sponge are vacuoles
resulting from dead neurons.
 Prions are composed of a single glycoprotein
with a molecular weight of 27,000-30,000.
 Prion proteins are encoded by a single cellular
gene.
This gene is found in equal numbers in the cells
of both infected and uninfected animals.
 The amount of prion protein mRNA is the same
in uninfected as in infected cells.
In view of these findings, posttranslational
modifications of the prion protein are hypothesized to be
the important distinction between the protein found in
infected and uninfected cells.
There is evidence that a change in the conformation
from the normal alpha-helical form to the abnormal
beta-pleated sheet form is the important modification.
The abnormal form then recruits additional normal
forms to change their configuration, and the number of
abnormal pathogenic particles increases.
When these proteins are in the normal,
alpha-helix configuration, they are
nonpathogenic.
 But when their configuration changes to a
beta-pleated sheet, they aggregate into
filaments, which disrupts neuronal function
and results in the symptoms of disease.
 Prions are highly resistant to inactivation by
ultraviolet light, heat, formaldehyde and
nucleases .
They are inactivated by hypochlorite, NaOH,
and autoclaving.
 Because they are normal human proteins, they
do not elicit an inflammatory response or an
antibody response in humans.