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7/31/2019 Viral Pathogenesis 2012
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Viral Pathogenicity
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Definitions
Pathogenicity: ability to cause
disease
Pathogenesis: means by whichorganism produces disease in host
Virulence: capacity to produce
disease
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Infection:
Entry of virus into the body,produces no symptoms or transientsymptoms due to local irritation
Infection Vs Disease
Disease:
Virus at Target organ, producessigns and symptoms associated with
disease
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Viral Infection Usually a form of symbiosis
Disease usuall results roinconclusive negotiations for symbiosis,an overstepping of the line by one side
or the other, a biologicmisinterpretation of border
Lewis Thomas
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Viral Disease
Effect of virus on the host
Effect of the host response
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InfectionIncubation Time:
Period of viral dissemination
o s gns or symp oms May be short
Disease at portal of entry May be long
Disease at a distant target organ
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Incubation Period: Other Factors Direct intravascular infection
Amount/Dose of virus
Long periods mechanism are poorlyunderstood
Persistent infectionDelayed lysis of cell or not lysedLate or no immune response
Mutation in host genome
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Response To Viral Infection:
No effect
Infection Vs Disease
Disease and/or death
Loss of growth Control
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Patterns of Disease:
Localised
Disease
Systemic
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Mechanism Of ViralPathogenesis
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Implantation at portal of entry
Local replication
Mechanism: Viral Pathogenesis
Spread to target organs
Spread to the sites for viralshedding into atmosphere
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Implantation at portal of entry
Viruses are carried to the body by all
possible routes (air, food, bites, anycontaminated object)
Therefore, all possible site of infection
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Implantation at portal of entry
4 major transmission site
- Respiratory Tract
- Gastrointestinal Tract- Skin
- Genital Tract
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Portals of Entry
Outcome:
Dose, Infectivity,
Virulence, Location
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Implantation at portal of entry
Certain variable may influence outcome
(Subclinical/mild/severe/lethal)
- Dose- Infectivity
- Virulence- Location
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Implantation at portal of entry
Local replication
Mechanism: Viral Pathogenesis
Spread to target organs
Spread to the sites for viralshedding into atmosphere
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Local replication
Successful implantation may be followed bylocal replication and local spread
Spread: intracellular or extracellular
Intracellular spread protects virus from Abresponse
Most viruses spread extracellular except(herpesviruses, paramyxoviruses & poxviruses
both)
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Local Infection
Intracellular or
extracellular
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Pathogenesis Of Selected Virus Infection: LocalizedInfections
DiseaseSite of
ImplantnRoute of
Spread
Target
Organ
Site of
Shedding
InfluenzaRespiratory
TractLocal
Respiratory
Tract
Respiratory
Tract
CoryzaRespiratory
TractLocal
Respiratory
Tract
Respiratory
Tract
GastroenteritisAlimentary
TractLocal
Alimentary
Tract
Alimentary
Tract
Warts Skin & Mucosa LocalSkin &
Mucosa
Skin &
Mucosa
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Implantation at portal of entry Local replication
Mechanism: Viral Pathogenesis
Spread to target organs
Spread to the sites for viralshedding into atmosphere
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Spread to target organs Directly
Blood
Neural
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Spread to target organs
Spread beyond adjacent cells lymphatic/ mucous/ migratory cells(lymphocytes and macrophages)
Establishment of infection at portal of
entry localised disease
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Dissemination from portal ofEntry for systemic spread
Blood stream
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Spread Via Blood Stream
shorter duration &less virus
longer duration
& more virus
eg. Polio,
smallpox,
measles
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Dissemination from portal ofEntry for systemic spread
Blood stream
Neural
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Neural Spread
thru nerves orperineural cells
Eg. Rabies,
some herpes& polioviruses
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Spread Of Picornavirus During Infection
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Balance between Host and Virusdefences
Multiplication in Target organ
Systemic host defence responses-Innate Immune response
-Interferons and Antibodies-Local factors
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Mechanism of Disease at Target
Infecting cells to produce dysfunction
Toxic products of Viral replication
o c ro uc o ce necro
Lymphokines and Inflammatory mediators
Immunosuppression
Sec Infections
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Implantation at portal of entry
Local replication
Mechanism: Viral Pathogenesis
Spread to target organs
Spread to the sites for viralshedding into atmosphere
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Spread Via Blood Stream
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During viraemia:
virus found free in blood (entero, toga)
cell associated (HIV, EBV, CMV, VZV,
measles, mumps, rubella)
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Neural Spread
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Respiratory tract
Alimentary tract
Blood stream
Shedding of Virus
Milk
Urine Saliva
Germ cells
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Horizontal
(Host Host of same generation)
Direct
Virus Transmission
Indirect-Food, Water-Vector-mediated-Needles
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Vertical(Host Progeny)
Transplacental
Virus Transmission
ru e a, , arvov rus
Perinatal(HIV, HBV)
Via Breast milk(HIV, HTLV)
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Routes of Infection in
the Fetus & Neonate
O I l d Eff i C i l
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Organ Involvement and Effects in Congenital
Rubella
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Fetal vulnerability
Rapid development
Congenital Infections
Immature immune response
Placental barrier-Viremia transmitted-Interferons stopped
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Non Viral Factors
Factors that modify Viral
Pathogenesis
Viral Factors
Host-Virus Interactions
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Lack of Virus receptors
Age
Metabolic State
Non Viral Factors (Host)
Malnutrition Vitamin A deficiency Pregnancy
Altered Immune response- Impaired (genetic, acquired, iatrogenic)
- Enhanced (autoimmunity)
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Immunological factors
-Circulating Antibodies-Natural Innate immunity-
Non Viral Factors (Host)
Non Specific Systemic factors-Local and physical barriers-Hormones, Temperature etc
Vi l F t
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1. Dose
2. Route of entry
3. Replication efficiency
4. Virulence
Viral Factors
(genes with enhance viral replication,modification of host defensemechanism, intrinsic cell killing ability)
5. Ability to Impede Immune response(Antigenic Drift / Antigenic shift)
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Antigenic Drift & Antigenic Shift
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Change Rearrange Disappear Reappear
Drift Gradual change Due to oint mutations in H & N
Happens to both A & B viruses
Shift
Occurs through reassortment of genes
Sudden change Explosive spread Only influenza A viruses
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H t Vi l I t ti
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Acute Infections
Persistent Infections
Host-Viral Interactions
H st Vi l Int ti ns
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Acute Infections(eventually eliminated from host)
-Hit and Run
Host-Viral Interactions
short IP, poor long term protectioncommon cold, more than 1 serotype
-Systemiclonger IP, good long term protectionmeasles, rubella, VZV, mumpsusually 1 serotype
Host Viral Interactions
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Persistent Infections-Latent Infection
-Chronic Infection-Chronic Infection with Neoplasia
Host-Viral Interactions
site of persistent is important way to evade host IR outcome can change depend on state
of individual
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Site of persistent HSV neuron
EBV B cells HHV-8 T cells
HBV liver cells
Dysplasia Cervix
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How do viruses evade Immune response?
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Latent Infection
Mutation
Inhibition o I une reco nition
How do viruses evade Immune response?
Target Host Cytokines
Lysis of Immune cells
Inhibition of Complement Response
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URTI
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URTI