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Chair of Medical Biology, Microbiology, Virology, and
Immunology
STRUCTURE,
CLASSIFICATION AND
PHYSIOLOGY OF VIRUSES
RNA-VIRUSES
Viruses are small obligate intracellular
parasites, which by definition contain either a RNA or
DNA genome surrounded by a protective, virus-coded
protein coat.
Viruses are unable to generate energy.
As obligate intracellular parasites, during
replication, they fully depend on the complicated
biochemical machinery of eukaryotic or
prokaryotic cells.
A complete virus particle is called a virion.
The main purpose of a virus is to deliver
its genome into the host cell to allow its
expression (transcription and translation) by the
host cell.
Classification
DNA-Containing Viruses
Hepadnaviridae
Parvoviridae
Papovaviridae
Adenoviridae
Herpesviridae
Poxviridae
Iridovoridae
Classification
RNA-Containing Viruses
Picornaviridae
Paramyxoviruses
Caliciviridae
Orthomyxoviruses
Togaviruses
Bunyaviridae
Flaviviridae
Arenaviridae
Coronaviridae
Reoviridae
Rhabdoviridae
Birnaviridae
Filoviridae
Retroviridae
Some Useful Definitions in Virology
Capsid: The symmetric protein shell that encloses the nucleic
acid genome. Often, empty capsids are by-products of the
viral replicative cycle.
Nucleocapsid: The capsid together with the enclosed nucleic
acid.
Structural units: The basic protein building blocks of the
capsid.
Capsomeres: Morphologic units seen in the electron
microscope on the surface of virus particles. Capsomeres
represent clusters of polypeptides, which when completely
assembled form the capsid.
Structure of viruses
A – naked, not containing an envelope aroud capsid
B – enveloped, containing an envelope around the
capsid
The helical structure of the rigid tobacco mosaic virus rod
In the replication of
viruses
with
helical
symmetry, identical protein
subunits (protomers) selfassemble into a helical array
surrounding the nucleic
acid, which follows a similar
spiral
path.
Such
nucleocapsids form rigid,
highly elongated rods or
flexible filaments;
Icosahedral Symmetry
An icosahedron is a polyhedron
having 20 equilateral triangular
faces and 12 vertices
Lines through opposite vertices
define axes of fivefold rotational
symmetry:
all
structural
features of the polyhedron
repeat five times within each
360° of rotation about any
of the fivefold axes.
Combined symmetry
Replication of poliovirus, which containing an RNA genome
Cultivation of Viruses
A. Chick Embryos: Virus
growth in an embryonated
chick egg may result in the
death of the embryo (eg,
encephalitis
virus),
the
production of pocks or
plaques
on
the
chorioallantoic
membrane
(eg,
herpes,
smallpox,
vaccinia), the development of
hemagglutinins
in
the
embryonic fluids or tissues
(eg, influenza), or the
development of infective
virus (eg, polio virus type 2).
Cultivation of Viruses
B. Tissue Cultures:
Primary cultures are made by dispersing cells (usually
with trypsin) from host tissues. In general, they are unable
to grow for more than a few passages in culture, as
secondary cultures.
- Diploid cell strains are secondary cultures which have
undergone a change that allows their limited culture (up to
50 passages) but which retain their normal chromosome
pattern.
- Continuous cell lines are cultures capable of more
prolonged (perhaps indefinite) culture which have been
derived from cell strains or from malignant tissues They
invariably have altered and irregular numbers of
chromosomes.
Cell Cultures
HeLA,
Hep-2,
Detroit-6,
KB,
Vero,
Fibroblasts of human embryou,
Kidney of rhesus monkey,
WI-38,
RD,
Primary cultures of chiken fibroblasts
Morphologic and Structural Effects
1 The cytopathic effect, or necrosis of cells in the tissue culture (polio-,
herpes-, measles-, adenovirus, cytomegalovirus, etc).
2 The inhibition of cellular metabolism, or failure of virus-infected
cells to produce acid (eg, enteroviruses).
3 The appearance of a hemagglutinin (eg, mumps, influenza) or
complement-fixing antigen (eg, poliomyelitis, varicella, measles).
4 The adsorption of erythrocytes to infected cells, called hemadsorption
(paramfluenza, influenza). This reaction becomes positive before
cytopathic changes are visible, and in some cases it is the only means of
detecting the presence of the virus
5 Interference by a noncytopathogenic virus (eg, rubella) with
replication and cytopathic effect of a second, indicator virus (eg,
echovirus).
Morphologic and Structural Effects
6 Morphologic transformation by an oncogenic virus (eg, SV40, Rous
sarcoma virus), usually accompanied by the loss of contact inhibition and the
piling up of cells into discrete foci Such alterations are a heritable property of
the transformed cells.
7 Formation of syncytia, or polykaryocytes, which are large cytoplasmic
masses that contain many nuclei (poly, many; karyon, nucleus).
8 Alteration of cytoskeleton organization by virus infection.
9 Genotoxic Effects (Chromosome damage may be caused directly by the
virus particle or indirectly by events occurring during synthesis of new viral
macromolecules (RNA, DNA, protein).
10 Inclusion Body Formation (They may be situated in the nucleus
(herpesvirus), in the cytoplasm (pox virus), or in both (measles virus)
Orthomyxovirus Family
The name myxovirus was originally applied
to influenza viruses. It meant virus with an
affinity for mucins.
A model of the influenza virion
Types: A, B, C
Influenza A:
In Birds
–16 H variants
–9 N variants
In Humans
–3 H variants
(H1, H2, and
H3)
–2 N variants
(N1 and
N2) H2N2,H2N3
Subtypes
: H1N1,
Influenza Viruses:
Antigenic Shift
Avian
Reservoir
Human
virus
Avian
virus
Other
mammals?
Swine
New
Reassorted
virus
Influenza Viruses:
Antigenic Drift
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Gradual accumulation of
mutations that allow the
hemagglutinin to escape
neutralizing antibodies (Point
mutation in HA gene)
Epidemic strains thought to have
changes in three or more
antigenic sites
Influenza Vaccines
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Whole virus vaccine: inactivated virus
vaccine grown in embryonated eggs; 7090% effective in healthy persons <65 years
of age, 30-70% in persons ≥65 years
Split virus vaccine: previously associated
with fewer systemic reactions among the
elderly and children <12 years
Subunit vaccine: composed of H and N
Live, attenutated influenza virus vaccines
under development
Family Paramyxoviridae
Genes:
Morbillivirus – measles virus,
Respirovirus – parainfluenza virus
(serotypes 1 and 3)
Rubulavirus - mumps virus,
parainfluenza virus
2, 4а, 4b),
Pneumovirus – RS-virus
(serotypes
PARAMYXOVIRUSES
pleomorphic
HN/H/G glycoprotein
SPIKES
F glycoprotein
SPIKES
helical nucleocapsid (RNA minus
NP protein)
lipid bilayer membrane
polymerase complex
M protein
STRUCTURE-PARAMYXOVIRUSES
Cell fusion. In the course of infection, paramyxo-
viruses cause cell fusion, long recognized as giant cell
formation.
MUMPS (Epidemic Parotitis)
Mumps is an acute contagious disease
characterized
by
a
nonsuppurative
enlargement of one or both of the parotid
glands, although other organs may also be
involved.
Properties of the Virus: The mumps virus
particle has the typical paramyxovirus
morphology. Typical also are the biologic
properties of hemagglutination, neuraminidase,
and hemolysin.
Epidemiology
The disease reaches its highest incidence in
children age 5-15 years, but epidemics occur
in army camps.
Humans are the only known reservoir of
virus.
The virus is transmitted by direct contact,
airborne droplets, or fomites contaminated
with saliva and, perhaps, urine. The period of
communicability is from about 4 days before
to about a week after the onset of symptoms.
Pathogenesis and Pathology
The virus travels from the mouth to the
parotid gland, where it undergoes primary
multiplication. This is followed by a generalized
viremia and localization in testes. ovaries,
pancreas, thyroid, or brain.
The ducts of the parotid glands show
desquamation
of
the
epithelium,
and
polymorphonuclear cells are present in the
lumens. There are interstitial edema and
lymphocytic infiltration.
Orchitis
PARAINFLUENZA VIRUS
The
parainfluenza
viruses
are
paramyxoviruses with morphologic and biologic
properties typical of the genus.
They grow welt in primary monkey or human
epithelial cell culture but poorly or not at all in
the embryonated egg. They produce a minimal
cytopathic effect in cell culture but are
recognized by the hemadsorption method.
Laboratory diagnosis may be made by the HI,
CF, and Nt tests.
PIV STRUCTURE
MEASLES (Rubeola)
Measles is an acute, highly infectious
disease
characterized
by
a
maculopapular
rash,
fever,
and
respiratory symptoms.
Properties of the Virus: Measles
virus is a typical paramyxovirus. It
lacks neuraminidase activity.
Measles virus
Koplik's spots
RESPIRATORY SYNCYTIAL (RS)
VIRUS
This labile paramyxovirus produces a
characteristic syncytial effect, the
fusion of cells in human cell culture. It is
the single most serious cause of
bronchiolitis and pneumonitis in infants.
Properties of the Virus: RS virus does
not hemagglutinate.
RSV- Structure
immunofluoresent stain
RSV- syncytium formation
Pathogenesis and Pathology
This disease is transmitted by
coughing, sneezing, sharing wash
cloths towels and other things with
someone with RSV.
This disease is
extremely serious
when it comes to
children and infants
under the age of 3 and
elders.
This disease can result
in death.
Symptoms for this disease are: sneezing,
runny nose, sore throat, low fever,
common cold symptoms just more severe.
Treatment:
Supportive
Fluids, oxygen,
respiratory support,
bronchodilators
Antiviral Agents
Ribavirin (Virazole), a
synthetic guanosine
analogue, given as an
aerosol
RSV Bronchiolitis- clinical features
Prophylaxis
 Combination live virus
(measles-mumps-rubella)
vaccines
 Live attenuated measles virus
vaccine effectively prevents measles.
Genera of Picornaviruses
Enterovirus
Polio, types 1-3
Coxsackie A ,
types
1-24
Coxsackie B, types 1-6
Echo, types 1-34
Other enteroviruses,
types 68-71
Rhinovirus,
1-115
types
Diseases of the human (and other) alimentary tract (e.g.
polio virus)
Disease of the nasopharyngeal region (e.g. common cold
virus)
Cardiovirus
Murine encephalomyocarditis, Theiler's murine
encephalomyelitis virus
Aphthovirus
Foot and mouth disease in cloven footed animals
Hepatovirus
Human hepatitis virus A
Others
Drosophila C virus, equine rhinoviruses, cricket paralysis
virus
RNA
Properties
of enteroviruses
Property
Size (nm)
Capsid form
Polypeptide
RNA type
Acid
Optimal temperature for
growth(oC)
Enteroviruses
22-30
Icosahedral
VP1, VP2, VP3,
VP4
‘+’, single stain
Stable
37
POLIOMYELITIS
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“Picornavirus”
3 types: Poliovirus
1,2,3
Ingested, spread
by alimentary
route: Commoner
in areas of poor
sanitation
Infants protected
by maternal
antibodies
Poliomielitis virus
Poliomyelitis is an acute infectious
disease that in its serious form affects
the central nervous system. The
destruction of motor neurons in the
spinal cord results in flaccid paralysis
(less than 0.1%). However, most
poliovirus infections are subclinical.
Morphology.
The virus is 30 nm in size and forms
intranuclear
inclusions.
The
virion
is
icosahedral and consists of a single sensestrand RNA and a protein capsid containing
32 spherical subunits (capsomeres).
Cultivation.
The poliomyelitis virus is
cultivated on kidney cells of
green African monkeys and on
diploid human cells devoid of
latent SV40 viruses.
The cytopathic effect is
attended by destruction and the
formation of granules in the
infected cells.
Transmission
 Fecal
– oral route: poor
hygiene, dirty diapers
(especially in day-care
settings)
 Ingestion via contaminated
food and water
 Contact with infected hands
 Inhalation of infectious aerosols
Nonparalytic Poliomyelitis (Aseptic
Meningitis). In addition to the above
symptoms and signs, the patient with
the
nonparalytic
form
presents
stiffness and pain in the back and neck.
The disease lasts 2-10 days, and
recovery is rapid and complete. In a
small percentage of cases, the disease
advances to paralysis.
Paralytic Poliomyelitis. The major
illness usually follows the minor illness
described above, but it may occur
without the antecedent first phase.
The predominating complaint is flaccid
paralysis resulting from lower motor
neuron damage. The maximal recovery
usually occurs within 6 months, with
residual paralysis lasting much longer.
Child with polio sequelae
Prevention
Both oral polio vaccine (OPV live,
attenuated， Sabin, 1957) and
inactivated poliovirus vaccine
(IPV, Salk, 1954) are avilable
IPV is used for adult
immunization and
Immunocopromised patients
Advantages and disadvantages of OPV
Advantages
Effectiveness
 Lifelong immunity
 Induction of secretory antibody response
similar to that of natural infection
 Possibility of attenuated virus circulating in
community by spread to contacts (indirect
immunization)(herd immunity)
 Ease of administration
 Lack of need for repeated boosters

Advantages and disadvantages of OPV
 Risk
Disadvantages
of vaccine-associated
poliomyelites in vaccine recipients
or contacts
 Spread of vaccine to contacts
without their consent
 Unsafe administration for
immunodeficient patients
Advantages and disadvantages of IPV
Advantages
 Effectiveness
 Good
stability during transport
and in storage
 Safe administration in
immunodeficient patients
 No risk of vaccine-related
disease