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3. Gastrointestinal Route
 Aka
“alimentary” or “fecal-oral”
 Viruses replicate in intestine
 Spread to new hosts through
contaminated food or water
 Picornaviridae (most), Caliciviridae,
Rotavirus
RNA Virus Families
PICORNAVIRIDAE (Picorna Means Small RNA!!)
• Hundreds of species viruses are prevalent world-wide.
• cause many serious diseases of animals and man.
• Foot and mouth virus first animal virus described (1898).
• Poliovirus is an important model:
- first animal virus purified and crystallized.
- first inactivated vaccine used (Salk 1950’s).
- first picornavirus to be sequenced.
- first infectious cDNA clone of an animal virus.
- first picornavirus structure to be solved.
PICORNAVIRUS PROPERTIES
• Capsids are small unenveloped 25 -30 nm icosahedra.
• Many resistant to pH 3 to 9.
• Plus sense single stranded RNA genomes (7400 bases).
• Genome is monopartite.
• RNA 5’ end has a covalently attached VPg (22-24 aa)
and 3’ end is polyadenylated.
• The 5’ end contains a highly structured (~740 nt)
untranslated region that contains several AUG’s.
• The naked RNA is sufficient for infection.
• The RNA is translated into a polyprotein that is cleaved
into Replication and Structural proteins.
• All picornaviruses replicate in the cytoplasm.
http://www.picornaviridae.com/
17 Genera as of 2011
Genus Enterovirus
- Poliovirus type member, 3 major types cause paralysis,
now called enterovirus C
-Coxsackie viruses-now enterovirus A, B
-rhinoviruses
Genus Hepatovirus
- Hepatitis A, contagious liver infections.
Genus Cardiovirus
- EMC group, cause heart and brain inflammation
acid labile, source is a rodent reservoir.
Genus Apthovirus
- Foot and mouth disease, most destructive in Africa.
Evolutionary “tree”- how ancient are picornaviruses????
Hepatitis A Virus (HAV)
Hepatovirus and liver disease
Acute, self-limiting liver disease
Fecal-oral transmission of HAV
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Hepatitis A Cases in Pennsylvania Rise to 510
Pittsburgh Blog « Green Onions Pulled From Chi-Chi's Menu
Nationwide | Main | Pittsburgh Holiday Happenings »
November 17, 2003
Hepatitis A Cases in Pennsylvania Rise to 510
The number of confirmed Hepatis A cases in Western Pennsylvania
have exceeded 500, including 3 deaths, in what has now become
the largest hepatitis A outbreak in U.S. history, according to the
Centers for Disease Control and Prevention. As a precaution, many
restaurant chains are now removing green onions from their menus
nationwide.
640 confirmed cases and 4 deaths
Traced back to onions from Mexico served in mild salsa during midOctober
General Features of Hepatitis A Infection
 Enterically transmitted (fecal/oral route).
 Multiplies in intestinal epithelial cells.
 Moves into the bloodstream and reaches the liver.
 After 15 to 50 days hepatitis symptoms appear.
 Transient hepatitis last at most a few weeks.
Often referred to as “infectious hepatitis”.
Only a single serotype exists.
Vaccine available since 1992
HAV time course
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Virus ingested
Primary replication in
intestinal lining?
Viremia
Virus shedding
Involvement of liver
Elevated enzyme
profile
Immune response
Good ways to
catch HAV
From 1 November 2012 to 30 April 2013, 15 confirmed cases of hepatitis A
virus (HAV) infections with subgenotype IB and identical RNA sequence, and
89 probable cases, have been reported in 14 EU/EFTA countries. All cases
have a travel history to Egypt.
Use of Molecular Epidemiology to Confirm a Multistate Outbreak of
Hepatitis A Caused by Consumption of Oysters
The enterovirus formerly
known as poliovirus
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Humans only natural host
Long history in our species
Water-borne
Usually causes mild diseaseoften with no real symptoms
All enteroviruses are
neurotropic
Disease progression
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Ingestion
Primary replication, lymph nodes
Primary viremia
95% asymptomatic
Secondary viremia and further
replication in other tissues
4-5% mild symptoms
Progression to CNS
Neurological symptoms-less
than 1%are
Paralytic cases even more rare
Virus shedding in feces
A 20th Century Problem-Why?
Important findings leading to the Control of Poliovirus
1908 - Karl Landsteiner transmitted
poliomyelitis from a boy to monkeys
and suggested that the disease was
caused by a virus.
1931- Sir Macfarlane Burnett found
demonstrated seriologically distinct
poliovirus strains. Infection with
poliovirus was shown to be common
but paralytic disease was rare. Three
major strains were found to be
responsible for paralysis.
John Enders found that poliovirus
could be grown in cell cultures. Won
the 1954 Nobel Prize.
Jonas Salk developed killed virus
vaccines. By 1954, two million
school children were vaccinated
with 80 -90 % effectiveness. By 1958,
nearly 450 million doses of vaccine
had been given.
1962 - Albert Sabin developed a live oral vaccine. The virus replicates
well in intestine and can be transmitted to others. In infants the virus is
excreted in feces where it is transmitted to other family members who
are protected.
Impact of vaccine
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Salk inactivated vaccine, injectable, 1955
 Sabin attenuated vaccine, oral, 1961-62
 OPV provides strong immunity
 “attenuated” vaccine
Eradication Initiative Begun 1988
 WHO,
UNICEF, CDC-goal: 2000
 Rotary International
 Private foundations
 Strategy includes:
Childhood coverage
National Immunization Days
Surveillance
Follow up
Milestones
 Western
Hemisphere polio-free 1994
 Europe polio-free 2002
 Pulse Polio campaign reduces cases in
India to 66 by 2005; 1979 worldwide
 India polio-free 2012
 Endemic polio in 3 countries: Nigeria
Pakistan Afghanistan
 Scattered elsewhere-introduced
Learn in Business and Global
Citizenship
February 11, 2013 at 1:00 PM
Bill Gates Says Expect Polio
Eradication by 2018, Measles
and Malaria, You're Next
Norwalk and Norwalk-like viruses
(Noroviruses) Caliciviridae
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School outbreak, Norwalk,
Ohio, 1968
Acute gastroenteritis
50% of 232 students and
teachers affected
Secondary attack rate of
32% among families
Virus particles discovered
in stool filtrate, 1972
Norovirus outbreaks reported on 2 cruise
ships that sailed the Caribbean
By Eliott C. McLaughlin, CNN
updated 4:50 PM EST, Fri January 31, 2014
Cruise passengers talk about Caribbean Princess trip
that returned to Houston early
Friday, January 31, 2014
Disney ship docks with 195 ill
Next week's cruise canceled to sanitize vessel
Saturday, November 30, 2002 Posted: 12:32 PM EST (1732 GMT)
Passengers of Disney's cruise ship Magic arrive Saturday in Port Canaveral, Florida.
CNN's Susan Candiotti reports Disney announced it will cancel the next tour of the cruise ship
Magic after confirming it is sailing with the Norwalk virus.
PORT CANAVERAL, Florida (CNN) -- Sunny skies greeted the Disney cruise ship Magic as it
docked here early Saturday, carrying 195 sick passengers and crew members.
The vessel had completed a cruise of the western Caribbean, during which 172 passengers and 23
crew members came down with what is believed to be Norwalk virus.
U.S. Centers for Disease Control and Prevention (CDC) spokesman Owen Grant said the agency
would decide by Monday whether stool samples collected from those complaining of
gastrointestinal illness would be tested. If the culprit is confirmed to be Norwalk, it would be the
second such outbreak on the cruise ship in as many weeks.