viral pathogenesis 2012

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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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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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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Certain variable may influence outcome

(Subclinical/mild/severe/lethal)

- Dose- Infectivity

- Virulence- Location


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Local replication





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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





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Spread to target organs Directly

Blood

Neural


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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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Local replication





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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


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


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

viral pathogenesis 2012

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