8/6/2019 Pathogenesis of Viral Infections
http://slidepdf.com/reader/full/pathogenesis-of-viral-infections 1/3
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
http://slidepdf.com/reader/full/pathogenesis-of-viral-infections 2/3
Vi
¡
l L¡
t¢
n£ ¤
H¢
p¢
s¥
i¦
pl¢
x Vi
us
8/6/2019 Pathogenesis of Viral Infections
http://slidepdf.com/reader/full/pathogenesis-of-viral-infections 3/3
Eff § ̈
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)