H S V - 1

H S V - 1H S V - 1

Biological propertiesBiological properties1.Morphology and structure1.Morphology and structure 1>120-200 nm1>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

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

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) )

PATHOGENESIS PATHOGENESIS

HSV-1 Ocular HSV-1 Facial

HSV-1 acute

herpetic

gingivostomatitis

HSV-1 Ear

HSV Whitlow

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

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

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

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

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

Attachment

Penetration

Retrograde Axonal Capsid Transport

Viral Production

Latency

Viron Budding

Recurrences

TYPES OF INFECTIONTYPES OF INFECTION Primary infectionPrimary infection Latent infectionLatent infection Recurrent infectionRecurrent infection Congenital and neonate infectionCongenital and neonate infection

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

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

Secondary infectionSecondary infection gains access to the gains access to the

distal axonal terminae of distal axonal terminae of sensory nervessensory 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 replication where further replication or latency can occuror latency can occur

Trigeminal Nerve                                                                                               

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

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

Secondary IRSecondary IR HSV antigen is taken up by HSV antigen is taken up by Lagerhan's Lagerhan's

cellscells and presented on and presented on MHC IIMHC II to to memory memory CD4+ Th cellsCD4+ Th cells

The anti-viral functions ofThe anti-viral functions of T-cells include T-cells include cytotoxicitycytotoxicity, , inhibition of viral growthinhibition of viral growth, , lymphokine secretionlymphokine secretion, and , and support of support of CD8+ and humoral responsesCD8+ and humoral responses

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

TRETMENTTRETMENTDrugDrug 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

VACCINEVACCINE inactivated virus preparations treated inactivated virus preparations treated

with formalin with formalin Adjuvanted subunit Vaccine Adjuvanted subunit Vaccine Skinner Vaccine Skinner Vaccine