8/6/2019 Pathogenesis of Viral Infections

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a ogenes s o ra n ec ons

Iceberg concept of Infection

Severe symptoms

Mild symptoms

Infection but no symptoms

Exposure but no infection

Pathogenesis of Viral Infections

Interaction between viral & host factors (lead to disease production)

Virus Transmission

Pathogenesis

Viral Tropism

Viruses tend to exhibit organ & cell specificities

Following viral infection, there are m any different patterns of localization &

dissemination

Determinants of viral tropism include

y  Presence of specific cell surface receptors for that virus

y  Presence of cellular protein required for viral replication

y  Physiologic factors

Viral Virulence

Not an absolute properly of a virus

Depends on

y  Viral strain y  Route of infection

y  Dose of virus

y  Host

o  Genetic susceptibility

o  Immune sufficiency

o  Age

y  Presence of cofactor

(agent that modulate interaction between virus & host)

o  Sexually transmitted infections potentiate infection by HIV

o  Repeated attacks by m alarial parasite potentiate development

of Burkitts lymphoma by Epstein-Barr virus

Viral Replication

Does not necessarily cause cell death

y  Interfere with normal cell functions (can be subtle)

y  Inhibition of cellular apoptosis (prolong cell life)

 Does not necessarily lead to new progeny virus

Abortive infections, Latent infections

Abortive Viral Infections Viral Latency

Incomplete viral replicative cycle

y  Cell may be non-permissive &

unable to support expression of 

all viral genes

y  Infecting virus may be defective

(lack some functional viral gene)

Example abortive poliomyelitis

(fever, malaise, drowsiness,

headache, nausea, vomiting,

constipation, sore throat, recovery

in few days)

Persistence of viral genome

y  No production of progeny virions

(virion in non-replicating state)

(no virus can be recovered

between recurrences)

y  Under specific stimuli, reactivates

to produce progeny virions

Local

stimuli

Systemic

stimuli

Injury to

tissues

innervated by

latently

infected

neurons

Bacterial/ viral

infections,

menstruation,

physical or

emotional

stress,

hormonal

imbalance

Permits persistence of virus in

presence of a fully developed

immune responses

Allow lifelong infection of host 

8/6/2019 Pathogenesis of Viral Infections

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8/6/2019 Pathogenesis of Viral Infections

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t ofHost Age

S©  sce 

 

 

 

y of ce  

 

   ce   ty   es 

  rese  ce of maternal antibodies 

Maturation of immune res 

onse with age 

Exposure to inf ection

Inf ections Befo  e Bi

 

th 

Most maternal viral inf ections do not result in viraemia & f etal involvement   

bility of virus to inf ect pregnant women &transmitted to f etus 

Stage of gestation at which inf ection occurs  

bility of virus to cause damage to f etus (directly or indirectly! 

 

Mechanism b "  which virus cause injuries to host 

Inhibiting host cell DN 

,# 

N 

, proteinsynthesis (eg. poliovirus! 

 

Insertion viral proteins into host cells plasma membrane 

y  Directly damage its integrity 

y  Promote cell fusion

y  Eg. $  IV, measles virus, herpes virus 

% 

ecognition of viral proteins on surface of host cells by immune system

(eg. liver cells inf ected with$ 

BV& 

 ' 

utoimmune disease (eg. Postinf ectious encephalomyelitis   measles, rubella)

Severe progressive disease after a long incubation period (2-20 years)

(eg. subacute sclerosing panencephalitis SSPE, caused by measles virus variant)

y  Due to failure of immune system to clear initial measles inf ectiony  Def ective viral replication owing to lac

( 

of production of 1 viral gene 

products 

Immunosuppression

y  HIV inf ections () 

D4 T lymphocytes)

y  Measles virus inf ection (multifactorial  compromised function of 0 

PCs,

helper cells, eff ector cells)

Compromising host antimicrobial def ense (lead to 2° inf ections)

y  Viral damage to respiratory epithelium allows subse1 

uent bacterial

pneumonias 

Lysis of host cells 

y  Liver cells (by yellow f ever virus)

y  Neurons (by poliovirus)

Killing of 1 cell type, causing death of other cells that depend on them

y  Degeneration of muscle cells 

Denervated by attac2 

of poliovirus on motor neurons 

Causing cell transformation (results in neoplastic growth)

y  HBV   hepatocellular carcinoma

y  HCV   hepatocellular carcinoma

y  HPV   cervical cancer, genital tumors, oropharygeal carcinoma

y  EBV   3 

frican Burkitts lymphoma, NPC, B-cell lymphoma

y  HTLV-1  4 

dult T-cell lymphoma

y  HHV-8   Kaposi sarcoma

Viral Shedding

5 

epresents the time which inf ected individual is inf ectiousto contacts 

May occur in

y  Respiratory tract

y  Alimentary tract

y  Blood stream

y  Semen/ genital tract

y  Milk

y  Urine 

y  Saliva

Does not occur in inf ections where human represent dead-end host (eg. rabies)

Occurs at diff erent stages of disease (depend on particular agent involved)

y  HSV sheds 

o  At prodrome 

o  During outbreaks 

o  During healing periods after outbreaks 

y  At random times (3-10d in the year)

There may be no noticeable symptoms at all

(subclinical shedding/ asymptomatic shedding)

Recovery f rom Viral Inf ections 

Cell-mediated immunity 

Humoral immunity 

Interf eron (& other lymphokines)