H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm...
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Transcript of H S V - 1 H S V - 1. Biological properties 1.Morphology and structure 1>120-200 nm 1>120-200 nm...
H S V - 1H S V - 1
Biological propertiesBiological properties
1.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 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
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
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 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
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
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
VACCINEVACCINE
inactivated virus preparations treated inactivated virus preparations treated with formalin with formalin
Adjuvanted subunit Vaccine Adjuvanted subunit Vaccine
Skinner Vaccine Skinner Vaccine