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Introduction to Medical Virology
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General properties of viruses
Classification of viruses
Pathogenesis of viruses
Laboratory diagnosis
Out line
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Introduction
y Virology is the bioscience for study of viral nature,
and the relationship between viruses and hosts.
y Viruses often cause serious diseases, relate to
some cancers and congenital deformities, also can
be used as tool for genetic engineering.
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Definition of Virus
Viruses may be defined as acellular organism whose
genomes consist ofnucleic acid, and
which obligately replicate inside host cells using host
metabolic machinery and ribosomes to form a pool of
components which assemble into particles called
VIRIONS.
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Viral Properties
y Viruses are inert (nucleoprotein ) filterableAgents
y Viruses are obligate intracellular parasites
y Viruses cannot make energy or proteinsindependent of a host cell
y Viral genome are RNA or DNA but not both.
y Viruses have a naked capsid or envelope withattached proteins
y Viruses do not have the genetic capability tomultiply by division.
y Viruses are non-living entities
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Consequences of Viral Properties
y Viruses are not living
y Viruses must be infectious to endure in nature
y Viruses must be able to use host cell processes
to produce their components (viral mRNA,protein, and identical copies of the genome)
y Viruses must encode any required processes notprovided by the cell
y
Viral components must self-assemble
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Size and Shape
y Methods
y Size of Viruses
y Shapes of Viruses
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Meth
ods of Analysis
size and shape can be described
Electron microscopy :The resolution is 5nm (1nm = 10-9 m)
X-ray crystallography
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Size of Viruses
A small virus has a diameter of about 20nm.
Parvovirus
A large virus have a diameter of up to 400nm.
Poxviruses
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Shape of Viruses
y Spherical
y Rod-shaped
y Brick-shaped
y Tadpole-shaped
y Bullet-shaped
y Filament
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Shapes of Viruses:Spherical
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Shapes of Viruses :Rod-shaped
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Shapes of Viruses :Brick-shaped.
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Tadpole-shaped
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Shapes of Viruses :Bullet-shaped
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Shapes of Viruses :Filament
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Structure of Viruses
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Structures compared
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Viriony the complete infectious unit of virus
particle
y
St
ruct
urally mat
ure, ext
racellularvirus particles.
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Virion
Capsid
Viral core
envelope
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Viral core
y Viral core
The viral nucleic acid genome, In the center of
the virion: Control the viral heredity and variation,responsible for the infectivity.
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Genome
y The genome of a virus can be either DNA or RNA
y DNA-double stranded (ds): linear or circularSingle stranded (ss) : linear or circular
y RNA- ss:segmented or non-segmented
ss:polarity+(sense) or polarity (non-sense)
ds: linear (only reovirus family)
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y Genomes may be either:
y (+) sense: Positive-sense viral RNA is identical to viral
mRNA and thus can be immediately translated into
protein by the host cell.
OR
y (-) sense: Negative-sense viral RNA is complementary
to mRNA and thus must be converted to positive-
sense RNA by an RNA Polymerase before translation.
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Viral Capsid
y The protein shell, or coat, that encloses the
nucleic acid genome.
y
Functions: a. Protect the viral nucleic acid.b. Participate in the viral infection. c. Sharethe antigenicity
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Nucleocapsidy The core of a virus particle consisting of the
genome plus a complex of proteins.
y complex of proteins = Structural proteins
+Non- Structural proteins (Enzymes&Nucleic acid binding proteins)
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Symmetry of Nucleocapsid
y Helical
y Cubic /Icosahedraly Complex
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Helical symmetry
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Helicaly California Encephalitis Virus
CoronavirusHantavirusInfluenza Virus (Flu Virus)
Measles Virus (Rubeola)Mumps VirusParainfluenza VirusRabies VirusRespiratory Syncytial Virus(RSV)
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Cubic or icosahedral symmetry
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Icosahedral
y Adeno-associated Virus (AAV)AdenovirusB19Coxsackievirus - A
Coxsackievirus - BCytomegalovirus (CMV)Eastern Equine Encephalitis Virus(EEEV)EchovirusEpstein-Barr Virus (EBV)Hepatitis A Virus (HAV)
Hepatitis B Virus (HBV)Hepatitis C Virus (HCV)Hepatitis Delta Virus (HDV)Hepatitis E Virus (HEV)
y Herpes Simplex Virus 1 (HHV1)Herpes Simplex Virus 2 (HHV2)Human Immunodeficiency Virus (HIV)Human T-lymphotrophic Virus (HTLV)
Norwalk VirusPapilloma Virus (HPV)Polio virusRhinovirusRubella VirusSaint Louis Encephalitis VirusVaricella-Zoster Virus (HHV3)
Western Equine Encephalitis Virus (WEEV)Yellow Fever Virus
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Complex Virus Structures
y A well known example is the tailed
bacteriophages such as T4.y The head of these viruses is cubic with
a triangulation number of 7. This is
attached by a collar to a contractile tail
with helical symmetry.
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T4 Bacteriophage
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Properties of naked virusesy Stable in hostile environment
y Not damaged by drying, acid, detergent, and heat
y
Released by lysis of host cellsy Can sustain in dry environment
y Can infect the GI tract and survive the acid and
bile
y Can spread easily via hands, dust, fomites, etc
y Can stay dry and still retain infectivity
y Neutralizing mucosal and systemic antibodies are
needed to control the establishment of infection
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Naked viruses(Non Enveloped)
y Adeno-associated Virus (AAV)Adenovirus
B19Coxsackievirus - ACoxsackievirus - BEchovirus
Hepatitis A Virus (HAV)Hepatitis E Virus (HEV)Norwalk Virus
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Envelope
yA lipid-containing membrane thatsurrounds some viral particles.
y It is acquired during viral maturation by abudding process through a cellularmembrane, Viruses-encoded glycoproteinsare exposed on the surface of theenvelope.
y Not all viruses have the envelope, andviruses can be divided into 2 kinds:enveloped virus and naked virus.
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Functions of envelope
y Antigenicity
some viruses possessneuraminidase
y Infectivity
y Resistance
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Envelope
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Properties of enveloped viruses
y Labile in dry , arid environment
y
Damaged by drying, acid, detergent,and heat
y Pick up new cell membrane during
multiplication
y Insert new virus-specific proteins afterassembly
y Virus is released by budding
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Consequences of Properties for enveloped
viruses
y Must stay moist
y Must not infect the GI tract for survival
y Must be transmitted in the protective,
droplets, secretions, blood and body fluids
y Must reinfect another host cell to sustain
y Humoral and cell-mediated immunity areneeded to control the infection
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Enveloped
y California Encephalitis Virus
y Coronavirus
y Cytomegalovirus (CMV)
y Eastern Equine Encephalitis Virus(EEEV)
y Epstein-Barr Virus (EBV)
y HantavirusHepatitis B Virus (HBV)Hepatitis C Virus (HCV)Hepatitis Delta Virus (HDV)
Herpes Simplex Virus 1 (HHV1)y Rotavirus
y Rubella Virus
y Saint Louis Encephalitis VirusSmallpox Virus (Variola)Vaccinia Virus
y Herpes Simplex Virus 2 (HHV2)Human Immunodeficiency Virus(HIV)Human T-lymphotrophic Virus(HTLV)
Influenza Virus (Flu Virus)Molluscum contagiosumPapilloma Virus (HPV)Polio virusRhinovirusVaricella-Zoster Virus (HHV3)Venezuelan Equine Encephal. Vir.
(VEEV)Western Equine Encephalitis Virus(WEEV)Yellow Fever Virus
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Replication of Viruses
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Replicative cycle
y As obligate intracellular parasites, Virus must enter and
replicate in living cells in order to reproduce themselves.
y This growth cycle involves specific attachment of virus,penetration and uncoating, nucleic acid transcription, protein
synthesis, matureation and assembly of the virions and their
subsequent release from the cell by budding or lysis
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Virus replication: general
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Initiation Phase
y Attachment
y Penetration
y Uncoating
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Attachment/Adsorption
y Virus attaches to the cell surface. Attachment is
via ionic interactions which are temperature-
independent.
y
Viral attachment protein recognizes specificreceptors on the cell surface (These may be
protein or carbohydrate or lipid components of
the cell surface).
y Cells without the appropriate receptors are notsusceptible to the virus.
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PENETRATION
(Virus enters the cell)
y Virions are either engulfed into vacuoles by
endocytosis or the virus envelope fuses with the
plasma membrane to facilitate entry
y Enveloped viruses
y Non-enveloped viruses
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Fusing
y (A) Entrybyfusingwith
theplasmamembrane.
Someenveloped virusesfusedirectlywiththe
plasmamembrane.Thus,
theinternalcomponents
ofthevirionareimmediatelydelivered tothecytoplasmofthecell.
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HIV
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Endocytosisy (B) Entry viaendosomes at thecellsurface
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influenza virus
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Enveloped virusesy Some enveloped viruses require an acid pH for
fusion to occur and are unable to fuse directly withthe plasma membrane.
y These viruses are taken up by invagination of
clathrin coated pits into endosomes. As theendosomes become acidified, the latent fusionactivity of the virus proteins becomes activated bythe fall in pH and the virion membrane fuses with the
endosome membrane.This results in delivery of theinternal components of the virus to the cytoplasm ofthe cell
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Non-enveloped viruses
y Non-enveloped viruses may cross the plasma
membrane directly
y may be taken up via clathrin-coated pits into endosomes.They then cross (or destroy) the endosomal membrane.
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UNCOATING
y Nucleic acid has to be sufficiently uncoated that virus
replication can begin at this stage. When the nucleic
acid is uncoated, infectious virus particles cannot be
recovered from the cell - this is the start of the ECLIPSE
phase - which lasts until new infectious virions are madey Uncoating is usually achieved by cellular proteases opening
up the capsid
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genome synthesis
mRNA production
protein synthesis
BIOSYNTHESIS
Fl f d i h li i f
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Flow of events during the replication of
Hepadna viruses
Fl f d i h li i f
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Flow of events during the replication of
herpesviruses
Fl f t d i g th
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Flow of events during the
replication of reoviruses.
Fl f t d i g th
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Flow of events during the
replication of togaviruses
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Flow of events during the replication of
orthomyxoviruses and paramyxoviruses.
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Flow of events during the replication
of retroviruses
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Maturation assembly release
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Maturation
y The stage of viral replication at which a virus particle
becomes infectious; nucleic acids and capsids are
assembled together.
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ASSEMBLY
y The stage of replication during which all the structural
components come together at one site in the cell and
the basic structure of the virus particle is formed.
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RELEASE
y Disintegration : naked virus cause the host cell
lysis
y Budding: enveloped viruses
y Budding viruses do not necessarily kill the cell.Thus,some budding viruses may be able to set up persistence
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Assembly
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Products of viral replication
y Viriony DEFECTIVE VIRUS
y ABORTIVE INFECTION
y integration
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y DEFECTIVEVIRUS
deficiency in some aspects of replication, but
interfering the replication of normal viruses
y ABORTIVE INFECTION
When a virus infects a cell (or host), but cannot
complete the full replication cycle ( not biosynthesizetheir components or not assemble virions.), i.e. a non-productive infection.
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INTERFERENCE
y Interferon, IFN
y Defective interfering particle, DIP
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Mutation
yMutant
yVariant
ytemperature sensitive(ts)
mutant
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Interactionswhen two genetically distinct viruses infect a cell
3 different phenomena can ensue
y Recombination /Reassortment
y Complementation
y Phenotypic mixing
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yRecombination
dsDNA viruses
y
Reassort
ment
( segment
ed genomes)RNA viruses: influenza virus
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Complementation
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Phenotypic mixing
y The genome of virus A can be coated with the surface protein
of virus type B
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Prions
y Prions are rather ill-defined infectious agents believedto consist of a single type of protein molecule with nonucleic acid component. Confusion arises from the factthat the prion protein & the gene which encodes it arealso found in normal 'uninfected' cells. These agentsare associated with diseases such as Creutzfeldt-Jakobdisease in humans, scrapie in sheep & bovinespongiform encephalopathy (BSE) in cattle.