1. No category

Introduction to viral infections
- a “Body Systems” approach
Learning objectives
• To list a representative set of viruses for each
target organ
• To show how all organs in the body are
susceptible
• To highlight viruses which are “multi-tropic” infecting several sites
• Show differential disease outcomes dependent
on sites of infection
What are “Body Systems”?
Anatomically definable zones
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•
•
•
•
•
•
•
•
Eye
Upper Respiratory Tract
LRT
Heart
Nervous system
Skin
GI
Liver
GU
Bone/joints
Immune system
Virus Infection site examples
Entry/Spread
• Respiratory tract (influenza, measles)
• Mouth (rota, polio, HAV)
• Genito-urinary tract (HIV)
• Eyes (adeno,HSV)
• Broken skin (into blood) (HSV, HBV, HIV)
Innate immunity
A 40 year old male sheep farmer from Hereford
who presented with pneumonia but was also found
to have pustules on his hands. He was diagnosed
as having ORF. He was vaccinating his sheep
against this disease and believes he must have
contracted it from scratches he got when dealing
with his flock.
ORF virus causes a common infection of sheep
(sometimes called sheep pox), it’s a parapoxvirus,
similar to the one that kills red squirrels.
Effective innate immunity means it takes an unusual
route of infection for this virus to infect a human, a
Zoonosis
Mutation of this virus could theoretically overcome
the innate response and become human to human
transmissable, leading to a new disease.
Courses of infection
The prodromal response to infection
Most common
symptoms of viral
infection are due to
the general effects
of innate immune
responses
6
Outcomes
• Inapparent/subclinical infection (polio)
• Chronic/Persistent/Latent infection (HCV/CMV/HSV)
• Acute infection/morbidity - clinical disease (influenza)
• Death/mortality (HBV, HIV, rotavirus)
Fig. 1.
Schneider-Schaulies J. J. Gen. Virol. 2000;81:1413-1429
©2000 by Society for General Microbiology
Antiviral Defences
Defence
•
•
•
•
•
Skin
Mucus
Ciliary epithelium
Gastric acid
Fluid flushing
– Urine, Saliva, Tears
• Fever
• Immunity
– Antigen-specific
• Antibody, T cells
– Non-specific
• Interferon, Macrophages, NK cells
URT
• Tonsillitis
EBV (Ad, Cx, HSV, Paraflu,
CMV, HIV)
• Cold
1/3 rhino, 1/3 (corona,
paraflu, flu, RSV, entero)
• LaryngoParaflu1 (2,3,MV,RSV,flu,
tracheo- rhino)
bronchitis
(croup)
URT
• Tonsillitis
• Cold
• Laryngotracheo(croup)
EBV (Ad, Cx, HSV, Paraflu,
CMV, HIV)
1/3 rhino, 1/3 (corona,
paraflu, flu, RSV, entero)
Paraflu1 (2,3,MV,RSV,flu,
Ad, rhino)
LRT
• Bronchiolitis
2/3 RSV (1/5 Paraflu,
flu, Ad rhino)
• Childhood pneumonia RSV (MV, VZV, paraflu,
flu, Ad,Cx)
• Influenza
Flu A (B,C, paraflu)
LRT
• Bronchiolitis
2/3 RSV (1/5 Paraflu,
flu, Ad rhino)
• Childhood pneumonia RSV (MV, VZV, paraflu,
flu, Ad,Cx)
• Influenza
Flu A (B,C, paraflu)
Nervous system
Encephalitis
• Primary
•
•
•
•
•
•
•
HSV, entero, arbo
(rabies, EBV, CMV,
HIV, flu, mumps, VZV)
Post-exanthem
MV, rubella, VZV
Subacute/chronic
HIV (SSPE (MV),
PML (JCV), CMV)
Polio
PV
Polio-like illness
Cx, ECHO
Myelitis
idiopathic (HSV,VZV, CMV,
EBV, HIV, HTLV1)
Guillain-Barré? idiopathic (EBV,CMV)
TSP
Nervous system
Encephalitis
• Primary
• Post-exanthem
• Subacute/chronic
• Polio
• Polio-like illness
• Myelitis
• Guillain-Barré
• TSP
HSV, entero, arbo
(rabies, EBV, CMV,
HIV, flu, mumps, VZV)
MV, rubella, VZV
HIV (SSPE (MV),
PML (JCV), CMV)
PV
Cx, ECHO
idiopathic (HSV,VZV,
CMV, EBV, HIV, HTLV1)
idiopathic (EBV,CMV)
HTLV
Digestive Tract
• Diarrhoea
• Warts and cancer
• Subclinical
Rota (Ad, SRSV,
Calici, Astro)
HPV
Polio
Polio? Nervous system?
Polio? Digestive Tract?
• Polio utilises the receptor CD155 (DAF)
• Migration of Polio from the gut to the CNS is
thought to be mediated by CD155+ mononuclear
cells in the blood
• OPV – an attenuated virus that generates both
IgG (blood) AND IgA (gut)
• IPV – A killed virus that only generates IgG
Polio? OPV?
Polio? IPV?
• OPV – cheap, room temperature stable
– “zero skill”, administration as oral drops
– Live virus,- can cause disease in immunodeficient children, can be spread
• IPV – cheap, requires cold storage
– Requires injection
– Dead virus,- no chance of disease
– Does not prevent infection of the gut
– Vaccinees can become asymptomatic carriers
Polio in Israel
• IPV is the standard vaccine (as in UK)
• Wild type polio detected in sewage samples
from >20 locations across Israel in 2012/3
QUIZ! What are they doing now?
Just a reminder, the Golan Heights form the border between
Israel and Syria.
Cardiovascular
• Myocarditis
• Pericarditis
Cx, ECHO (CMV, mumps,
EBV, HIV, flu, Ad)
Cx, ECHO (mumps, EBV,
flu, Ad)
Cardiovascular
• Myocarditis
• Pericarditis
Cx, ECHO (CMV, mumps,
EBV, HIV, flu, Ad)
Cx, ECHO (mumps, EBV,
flu, Ad)
Eye
• Conjunctivitis
• Keratitis
• Uveitis
Ads (enteros, HSV,
VZV, MV, Rubella)
HSV (VZV, MV,
Ads, Mumps)
(HSV, VZV)
Eye
• Conjunctivitis
• Keratitis
• Uveitis
Ads (enteros, HSV,
VZV, MV, Rubella)
HSV (VZV, MV,
Ads, Mumps)
(HSV, VZV)
Skin
•
•
•
•
•
Many conditions
Skin only, skin + deeper tissues/organs
Macules
Papules
Vesicles
Skin (2)
Maculo-papular rash
• Measles
MV
• German measles
Rubella virus
• Erythema infectiosum
Parvovirus B19
(5th Disease, slappedcheek syndrome)
Roseola infantum
HHV6
Purpuria/ haemorrhagic rash
• Measles
MV
• Haemorrhagic fevers
Lassa, Marburg, Ebola,
Crimean, Congo, Dengue)
Skin (2)
Maculo-papular rash
• Measles
MV
• German measles
Rubella virus
• Erythema infectiosum
Parvovirus B19
(5th Disease, slappedcheek syndrome)
Roseola infantum
HHV6
Purpuria/ haemorrhagic rash
• Measles
MV
• Haemorrhagic fevers
Lassa, Marburg, Ebola,
Crimean, Congo, Dengue)
Skin (3)
Papulo-vesicular rash
• Chicken pox
• Eczema herpeticum
• Hand-foot-mouth disease
Localized lesions
• Cold sores (Herpes labialis)
(genitalis)
• Warts
• Molluscum contagiosum
• Milker’s nodule
• Orf
VZV
HSV
Cx A16
HSV1
HSV1,2
HPV
MC virus
paravaccinia
Orf
Skin (3)
Papulo-vesicular rash
• Chicken pox
• Eczema herpeticum
• Hand-foot-mouth disease
Localized lesions
• Cold sores (Herpes labialis)
(genitalis)
• Warts
• Molluscum contagiosum
• Milker’s nodule
• Orf
VZV
HSV
Cx A16
HSV1
HSV1,2
HPV
MC virus
paravaccinia
Orf
Liver
• Hepatitis
• Acute
• Chronic
• HCC
HAV, HBV, HCV, (HDV,
HEV, CMV, EBV, YFV)
HBV, HCV (HDV)
Liver
• Hepatitis
• Acute
• Chronic
HAV, HBV, HCV, (HDV,
HEV, CMV, EBV, YFV)
HBV, HCV (HDV)
• HCC
HBV, HCV
GU system
• Genital ulcers - HSV HSV
• Urethritis - HSV
HSV
• Genital warts, CaCx - HPV HPV
Bone & Joints
• Infective arthritis
Parvo, rubella
HBV, mumps,
EBV, Ad, flu, arbo
Immune System
• Aids
HIV
• Glandular fever
EBV (CMV)
• BL
• ATL
HTLV
Immune System
• AIDS
HIV-1 & 2
• Glandular fever
EBV (CMV)
• BL
EBV
• ATL
HTLV1 & 2
Glands
• Glandular fever
EBV (CMV,HIV,HHV6)
• Parotitis
Mumps (Paraflu3, Cx, CMV)
-can lead to glandular (orchitis, oophoritis)
to neuro complications (meningitis)
• Cervical
(EBV, HIV, CMV)
lymphadenopathy
or
References
• Collier & Oxford Human Virology 2nd ed. (Esp.
Ch 4).
• Schneider-Schaulies “Cellular receptors for
viruses: links to tropism and pathogenesis” JGV,
81:1413-29, 2000