medical virology

8/6/2019 Medical Virology

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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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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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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.

medical virology

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