Polioviruses

DR. dr. Fadhilah, M.Kes

Department of Microbiology, Faculty of Medicine,

Hasanuddin University
2022
 Introduction
• Polio  a contagious viral illness that in its most severe
form causes nerve injury leading to:
– paralysis,
– difficulty breathing
– sometimes death.
• In the U.S., the last case of naturally occurring polio was in
1979.
• Adults who have been vaccinated who plan to travel to an
area where polio is occurring should receive a booster dose
of inactivated poliovirus vaccine (IPV).
• Immunity after a booster lasts a lifetime.
 Characteristics
• A member of the Picornaviridae virus family
• Small isometric particles, 30nm in diameter
• Containing a single molecule of single
stranded RNA.
• Rapidly inactivated by heat, formaldehyde,
chlorine, and ultraviolet light.
• 3 poliovirus serotypes: (PV-1, PV-2, and PV-3)
 Structure of the Virion
• Single-stranded RNA genome of
positive polarity surrounded by a
nonenveloped icosahedral protein
capsid.
• The mature virion is 30 nm in
diameter
• The capsid consists of 60 copies of
each of the four viral structural
proteins VP1 to VP4
• A deep surface depression, called
the “canyon” contains the site
for cell receptor binding (Colston
and Racaniello 1994, 1995; Belnap
et al. 2000; He et al.2000).
 Viral Cycle
• The viral cycle of PV
proceeds entirely in the
cytoplasm of the host
cell (Racaniello 2001).
• It is one of the fastest
known viral cycles,
lasting approximately
8h at 37oC in cell
culture.
 Poliomyelitis
• The term poliomyelitis is
derived from the Greek
words polios “gray,”
myelos “marrow,” 
results from the destruction
of neurons in the gray matter
of the anterior horn of the
spinal cord.
• Humans are the only natural
host of PV, and infections
with PV result in poliomyelitis
in only 1%–2% of cases.
 Transmission
• The virus enters through the mouth and
multiplies in the throat and gastrointestinal
tract.
• Virus may be excreted in nasopharyngeal
secretions for 1–2 weeks and in stools for 3–6
weeks, even in people who develop no
symptoms after infection.
• Occurs from person to person through the oral
and fecal–oral routes.
 Pathogenesis
• PV multiplies extensively in the tonsils and Peyer’s
patches (Bodian 1955)
• In humans, sensitivity to oral infection correlates
with CD155 expression in the intestinal epithelium,
including:
– The follicle-associated epithelium
– microfold M cells of Peyers patches,
– follicular dendritic cells and
– B cells of germinal centers within Peyer’s patches
(Iwasaki et al. 2002).
• The virus is released from lymphoid
tissues into the bloodstream 
viremia.
• The circulating virus invades the CNS
probably through the blood-brain
barrier
• In the CNS, the main target cell of PV:
– the motor neuron of the spinal cord
– the brain stem
• PV probably travels by cell-to-cell
spread
• The destruction of motor neurons
a consequence of PV replication 
paralysis.
 Epidemiology
• Before a vaccine was
availabla  infection with
wild poliovirus (WPV) was
common worldwide
• The incidence of
poliomyelitis in the United
States declined rapidly after
the licensure of inactivated
poliovirus vaccine (IPV) in
1955 and live oral polio
vaccine (OPV) in the 1960s.
 Clinical presentation
• Most poliovirus infections are asymptomatic
• About 25% cause minor illness with total
recovery.
• Paralysis may affect 1 or several limbs
• In severe cases it may result in quadriplegia,
respiratory failure, and rarely, death.
• Adults with poliovirus paralysis have more severe
disease and a worse prognosis than children.
 Post Polio Syndrome (PPS)
• After decades of clinical stability following acute paralytic
poliomyelitis  post-polio syndrome slowly progressive
muscle weakness
• PV persistence as cause of PPS is a consequence of:
– The presence of PV RNA sequences
– PV-related RNA
– anti-PV IgM antibodies
• Consistent with this hypothesis, PV can establish persistent
infections in human cell cultures of neuronal origin
(Colbre-Garapin et al. 1989, 2002; Pavio et al. 1996).
 Diagnosis
• Specimen  stool, oropharyngeal , rarely
detected in the blood or cerebrospinal fluid.
• Poliovirus is detected in specimens by cell
culture PCR  identify the serotype
• Because of new safety requirements in
handling polioviruses  CDC is the only
laboratory allowed to test specimens from a
suspected case of paralytic polio in the US
 Prevention
• The development of effective vaccines to prevent
paralytic polio was one of the major medical
breakthroughs of the 20th century.
• Two different kinds of vaccine are available:
– An inactivated (killed) polio vaccine (IPV) developed by Dr.
Jonas Salk and first used in 1955
– A live attenuated (weakened) oral polio vaccine (OPV)
developed by Dr. Albert Sabin and first used in 1961.
 Inactivated (killed) polio vaccine (IPV)
• Made by purifying viral preparations to a certain extent and then
inactivating viral
• Killed-virus vaccines prepared from whole virions generally stimulate
the development of circulating antibody
• Advantages:
– that there is no reversion to virulence by the vaccine virus and that
vaccines
– Can be made when no acceptable attenuated virus is available.
• Disadvantages:
– relatively brief immunity requiring boosting shots to maintain effectiveness,
– poor cell-mediated response,
– occasional hypersensitivity to subsequent infection.
 Attenuated Live-Virus Vaccines (OPV)

• Advantages:
– Acting more like the natural infection with regard to their effect on
immunity.
– They multiply in the host and tend to stimulate longer-lasting antibody
production
– induce a good cell-mediated response, and induce antibody
production
• Disadvantages:
– a risk of reversion to greater virulence, severe infection in
immunocompromised hosts,
– and limited storage and shelf life in some cases.
Have a look a bit closer!

HEPATITIS

Department of Microbiology,
Faculty of Medicine, Hasanuddin University
2022
 Viral hepatitis

Most common cause of liver disease Hepatitis A virus

Acute/chronic Liver inflammation due to virus infection

Hepatitis B virus

Boonstra 2012
 Viral Hepatitis Overview
Types of Viral Hepatitis

A B C D E
Source of feces blood/blood derived feces
virus body fluid

Route of fecal-oral Percutaneous fecal-oral

transmission Permucosal

Chronicity no yes yes yes no

Prevention pre- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
 Country with high HAV exposure rate
HAV: endemicity

Enterically-transmitted
Hepatitis viruses
WHO, 2009

HEV “Endemic Countries”

21
31-08-23
Enterically-transmitted Viral Hepatitis
HAV and HEV

Properties HAV:
• Family Picornavirus,
• single stranded RNA
• Virion 27 nm
• Non-enveloped: heat & acid stable
• Naked Icosahedral symmetry

HEV
• Family Caliciviridae
• ssRNA
• Virion 30-32 nm in diameter
• Non-enveloped
• Stability: heat stabile
 Route of Transmission

human human
Transmission routes are difficult to
separate!

What proportion is identified?

 Hepatitis A in semi-dried tomatoes

Australia: May 2009

• Increase in endemic hepatitis A infections (250 cases)
• Genotype 1B (300 nt), sequence shared with European network

France: 20 November- 17 February 2010

• Outbreak of HAV infections (49 cases)
• Genotype 1B (430 nt), 2 mutations compared to Australia

Netherlands: 16 February 2010

• Molecular surveillance detected 5 cases with identical HAV strain
• Genotype 1B (460 nt), identical to Australian, 3 nt difference France

Petrignani et al., EuroSurveillance 2010; Gallot et al., EID 2011

Hepatitis E Virus • Outbreaks of HEV reported
(HEV) • HEV causes > 25% of Sporadic
non-ABC hepatitis
“Endemic Countries”

Genotype 1

Genotype 2
26
 Mammalian HEV
Hepatitis E Virus
1 serotype
(HEV)

genotype 1 genotype 2 genotype 3 genotype 4

“Burma” “Mexico” “US / Swine” “China”

• Outbreaks • Sporadic cases

• (sub)tropical, developing • World wide (not in Africa)
countries, “high”
seroprevalence
• Water borne, fecol-oral, poor • Feco-oral? Food borne,
sanitation transfusion
• Reservoir: humans • Reservoir: pigs? wild boar
• Europe: travel related • Europe: indiginous (gt3)

31-08-23
I&I 2012 27
 RIVM 2012
Transmission of HEV
Genotype-3 in Japan
sashimi
namagimo

2003, Tei et al.,

• Consumption of uncooked
deer meat

2003, Matsuda et al.,

Consumption of uncooked
wild boar 28
 LABORATORY DIAGNOSIS
enterically-transmitted Hepatitis viruses :

• Liver function test : the increase of serum bilirubin, ALT and AST
level

• Detection of IgM antibody: A 4 fold rise of IgG antibody titer can

also be used

• Amplification of viral nucleic acid (PCR)

Chronic Hepatitis Viruses
 Hepatitis A Hepatitis B Hepatitis C

RNA DNA RNA

Transmission Fecal-oral Blood-to-blood Blood-to-blood
route contaminated food or - sexual contact - sexual contact
drinking water - blood transfusion - blood transfusion
- contaminated needles - contaminated needles
- vertical transmission - body piercings & tattoes
(mother>child) - intravenous drug use
- profession - vertical transmission
- profession

Vaccine YES YES NO

Target cells Hepatocytes Hepatocytes Hepatocytes

Kupffer cells

Symptoms Yes Often symptomatic Often asymptomatic

(adults) Fatigue, fever,
jaundice, ….

Prognosis Acute, self-limiting Acute (90-95% Acute (20-40%)

No permanent liver damage Chronic (5-10%) Chronic (60-80%)

Disease Fibrosis, cirrhosis, Fibrosis, cirrhosis,

pathogenesis liver failure, HCC liver failure, HCC

Boonstra 2012
Chronic Hepatitis Viruses

HBV :
• Family Hepadnaviridae, genus
orthohepadnavirus
• Circular dsDNA,
• Incomplete (+)ve strand
• DNA polymerase - reverse transcriptase
• Enveloped virion (acid sensitive)

HCV
• Family Flaviviridae, genus Hepacivirus
• Envelope virus
• ssRNA, linear, positive sense RNA
• Ether and acid sensitive
• Oncogenic
• Six serotype and multiple subtype.
• Genotypes 1a & 1b are the most
common
 Hepatitis B and C

HBV HCV

<1 %
1–2.4 %
8% - High 2.5–4.9 %
2-7% - Intermediate 5–10 %
> 10 %
<2% - Low No data

• 600 million chronic HBV/HCV patients

• 1 million die each year from HCC or liver failure
• 9th leading cause of death worldwide
 Laboratory Detections
• Detection of HBV/HCV from blood by electron microscope

• Serologic detection of HBV/HCV markers

• HBV/HCV detection by nucleic acid hybridization

technique like PCR

• Immunofluorescent staining → HBV core protein in the

nucleus of the host cell and infectious Dane particle in
the cytoplasm
 HBV Serologic markers
Marker Interpretations
HBsAg+ Hepatitis B acute/ chronic

Anti HBsAg+ Immune against HBV

IgM anti-HBc+ Titer higher: Hep B acute

Titer lower: Hep B chronic
IgG anti-HBc+ HBsAg - : pasca exposure
HBsAg + : Hep B chronic

HBeAg+ Hep B acute/ persistent

(cis = continued infection
state)

Anti-HBe+ Convalesence/ cis

HBV DNA Cis

(dot blot hybridization)
 SUMMARY. Characteristics of hepatitis viruses

Virus Hepatitis A Hepatitis B Hepatitis C

Family Picornaviridae Hepadnaviridae Flaviviridae
Genus Hepatovirus Orthohepadnavirus Hepacivirus
Virion nm, icosahedral 27 nm, spherical 42 calnm, spheri60
Envelope No Yes Yes
Genome ssRNA dsDNA ssRNA
Genome size kb 7.5 kb 3.2 kb 9.4
Stability Heat-and-acid -sensitiveAcid Ether-sensitive,
stable acid-sensitive

Transmission Fecal-oral Parenteral Parenteral

Prevalence High High Moderate
Ft dis.ulminanF Rare Rare Rare

Chronic disease Never Often Often

Oncogenic No Yes Yes
 SUMMARY. Characteristics of hepatitis viruses

Virus Hepatitis D Hepatitis E Hepatitis G

Family Unclassified 1
Caliciviridae Flaviviridae
Genus Deltavirus Unnamed Unnamed
Virion nm, spherical 35 nm, 30-32 nm, spherical60
icosahedral
Envelope Yes (HBsAg) No Yes
Genome ssRNA ssRNA ssRNA
Genome size kb 1.7 kb 7.6 kb 9.4
Stability sensitiveAcid- StableHeat- sensitiveEther-
Transmission Parenteral Fecal-oral Parenteral
Prevalence Low, regional Regional Moderate

Frequent In pregnancy ?

Chronic disease Often Never ?

Oncogenic ? No ?
THANK YOU