h s v - 1 h s v - 1. biological properties 1.morphology and structure 1>120-200 nm 1>120-200...

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Page 2: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral
Page 3: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Biological propertiesBiological properties

1.Morphology and structure1.Morphology and structure

1>120-200 nm1>120-200 nm

spherical spherical

icosahedral icosahedral

Page 4: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

2>core dsDNA linear 2>core dsDNA linear

(L segment and S(L segment and S

segment )segment )

3>capsid 162 3>capsid 162 capsomeres capsomeres

HSV-1 -capsid from 400kV Spot-scan Electron Cryomicroscopy

Page 5: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

4>envelope 4>envelope spike-like spike-like

glycoproteinsglycoproteins such as such as gB gC gD gB gC gD

gEgE

gG gH gI gG gH gI gLgL

gMgM

Page 6: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

CULTURECULTURE

HSV can replicationHSV can replication in many cellsin many cells

Such as kidney of rabit, Such as kidney of rabit,

lung of human embryo.lung of human embryo.

Cells infection by hsv become larger, Cells infection by hsv become larger, round,and has inclusion body in round,and has inclusion body in neucleus (neucleus (CPECPE) )

Page 7: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

PATHOGENESIS PATHOGENESIS

HSV-1 Ocular HSV-1 Facial

Page 8: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

HSV-1 acute

herpetic

gingivostomatitis

Page 9: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

HSV-1 Ear

HSV Whitlow

Page 10: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

ProcessProcess

1. Attachment 1. Attachment

gC and/or gB gC and/or gB attach to heparan attach to heparan sulfate proteoglycan sulfate proteoglycan (HS) on the cell (HS) on the cell surfacesurface

Herpes Simplex Virus-1 on a blood lymphocyte

Page 11: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

2.Penetration2.Penetration

1) 1) gDgD interact with cellular receptors interact with cellular receptors

2) 2) gC, gB, gDgC, gB, gD, with , with gHgH, and , and gLgL trigger trigger fusion of fusion of the viral envelopethe viral envelope (nuclear) (nuclear) and and the host cell plasma membranethe host cell plasma membrane

a pH-independent a pH-independent

Page 12: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

3Retrograde Axonal Capsid Transport 3Retrograde Axonal Capsid Transport

1 )HSV capsid undergoes rapid 1 )HSV capsid undergoes rapid transport by retrograde axonal flow to transport by retrograde axonal flow to the neuronal nucleusthe neuronal nucleus

2 ) 2 ) the capsidthe capsid fuses with the nuclear fuses with the nuclear membrane and membrane and the dsDNAthe dsDNA from the from the virion is injected into the nucleus via virion is injected into the nucleus via nuclear poresnuclear pores

Page 13: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

4 Packaging4 Packaging

empty capsid binds to empty capsid binds to an initiation an initiation sequencesequence

dsDNA is packaged into the dsDNA is packaged into the empty empty capsidcapsid

Page 14: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral
Page 15: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

5 Viron Budding5 Viron Budding viral capsids are enveloped at the viral capsids are enveloped at the

nuclear membranenuclear membrane transport vesiclestransport vesicles are transported are transported

through the cytoplasm of the infecte through the cytoplasm of the infecte cell(anterograde transport)cell(anterograde transport)

transport vesicles fuse with transport vesicles fuse with the plasma the plasma membranemembrane, releasing virions to the , releasing virions to the extracellular spaceextracellular space

Page 16: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Attachment

Penetration

Retrograde Axonal Capsid Transport

Viral Production

Latency

Viron Budding

Recurrences

Page 17: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

TYPES OF INFECTIONTYPES OF INFECTION

Primary infectionPrimary infection Latent infectionLatent infection Recurrent infectionRecurrent infection Congenital and neonate infectionCongenital and neonate infection

Page 18: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

MECHANISMMECHANISM

Primary infectionPrimary infection A key factor involved in the A key factor involved in the

intracellular edemaintracellular edema is the is the keratinocytes of the middle and basal keratinocytes of the middle and basal layers which are infected and undergo layers which are infected and undergo cytolysiscytolysis, resulting in the formation of , resulting in the formation of an an intraepidermal lesionintraepidermal lesion ,, which which rapidly evolves into an rapidly evolves into an epidermal epidermal lesionlesion, filled with , filled with yellowish fluidyellowish fluid, , causing causing displacement of chromatindisplacement of chromatin

Page 19: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Secondary infectionSecondary infection

gains access to the gains access to the distal axonal terminae distal axonal terminae of sensory nervesof sensory nerves and and travels by retrograde travels by retrograde axonal transport to axonal transport to neuronal cell bodiesneuronal cell bodies in in sensory ganglia, usually sensory ganglia, usually the trigeminal gangliathe trigeminal ganglia, , where further where further replication or latency replication or latency can occurcan occur

Trigeminal Nerve                                                                                               

Page 20: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Recurrences can be triggered by Recurrences can be triggered by

numerous environmental stimuli numerous environmental stimuli including including a common colda common cold, , feverfever,, severe sunburnsevere sunburn, , physical fatiguephysical fatigue, , emotional disturbanceemotional disturbance,, trauma trauma,, gastrointestinal disturbancesgastrointestinal disturbances,, menstruationmenstruation, , pregnancypregnancy,, debilitating debilitating illnessesillnesses,, oror food allergy food allergy

Page 21: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Immune responseImmune response

in primary infectionsin primary infections

antibodies to HSV antigens can be antibodies to HSV antigens can be detected within detected within 4 - 84 - 8 days ( days (IgM IgG IgAIgM IgG IgA))

viral antigens are presented on viral antigens are presented on dendritic cellsdendritic cells and and macrophagesmacrophages to to CD4+ Th1 cellsCD4+ Th1 cells

lysislysis of the Infected cells ---- of the Infected cells ----CD4+ T-CD4+ T-cellscells, , CD8 + T-cellsCD8 + T-cells, , NK cellsNK cells

Page 22: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

Secondary IRSecondary IR

HSV antigen is taken up by HSV antigen is taken up by Lagerhan's cellsLagerhan's cells and presented on and presented on MHC MHC IIII to to memory CD4+ Th cellsmemory CD4+ Th cells

The anti-viral functions ofThe anti-viral functions of T-cells T-cells include cytotoxicityinclude cytotoxicity, , inhibition of viral inhibition of viral growthgrowth, , lymphokine secretionlymphokine secretion, and , and support of CD8+ and humoral support of CD8+ and humoral responsesresponses

Page 23: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

DIAGNOSISDIAGNOSIS

Isolation and identification of virusIsolation and identification of virus Rapid diagnosis Rapid diagnosis

electroscope testelectroscope test

detect HSV antigendetect HSV antigen

detect DNA -----PCRdetect DNA -----PCR

Page 24: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

TRETMENTTRETMENT

DrugDrug Mode of Mode of Action Action 

Administered Administered FormForm

AcyclovirAcyclovir Disrupts the virusí ability to Disrupts the virusí ability to reproduce. (replicate) reproduce. (replicate)

Capsules or Tablets. Capsules or Tablets. Cream for use in oral Cream for use in oral herpes    Primary--> for 10 herpes    Primary--> for 10 days  days  Recurrent-> for 5 daysRecurrent-> for 5 days

ValacyclovirValacyclovir Disrupts the virusí ability to Disrupts the virusí ability to

reproduce. (replicatereproduce. (replicate Capsules or Tablets Capsules or Tablets Primary--> w/in 48 hours  Primary--> w/in 48 hours              --> for 10 days             --> for 10 days Recurrent -> w/in 24 hours  Recurrent -> w/in 24 hours 

                -> for 5 days                 -> for 5 days

FamciclovirFamciclovir Disrupts the virusí ability to Disrupts the virusí ability to

reproduce. (replicatereproduce. (replicate Capsules or Tablets. Capsules or Tablets. Cream for use in oral Cream for use in oral herpes Primary --> w/in 6 herpes Primary --> w/in 6 hours hours

             --> for 5 days             --> for 5 days

Page 25: H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm spherical spherical icosahedral icosahedral

VACCINEVACCINE

inactivated virus preparations treated inactivated virus preparations treated with formalin with formalin

Adjuvanted subunit Vaccine Adjuvanted subunit Vaccine

Skinner Vaccine Skinner Vaccine