3. Gastrointestinal Route3. Gastrointestinal Route

Aka “alimentary” or “fecal-oral”Aka “alimentary” or “fecal-oral” Viruses replicate in intestineViruses replicate in intestine Spread to new hosts through Spread to new hosts through

contaminated food or water contaminated food or water Picornaviridae (most), Caliciviridae, Picornaviridae (most), Caliciviridae,

RotavirusRotavirus

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 Capsids are small unenveloped 25 -30 nm icosahedra.icosahedra.• Many resistant to pH 3 to 9.Many resistant to pH 3 to 9.• Plus sense single stranded RNA genomes Plus sense single stranded RNA genomes (7400 bases).(7400 bases).• Genome is monopartite.Genome is monopartite.• RNA 5’ end has a covalently attached VPg (22-RNA 5’ end has a covalently attached VPg (22-24 aa) 24 aa) and 3’ end is polyadenylated.and 3’ end is polyadenylated.

• The 5’ end contains a highly structured (The 5’ end contains a highly structured (~~740 740

nt) nt) untranslated region that contains untranslated region that contains several AUG’s.several AUG’s.• The naked RNA is sufficient for infection.The naked RNA is sufficient for infection.• The RNA is translated into a polyprotein that is The RNA is translated into a polyprotein that is cleaved cleaved into Replication and Structural into Replication and Structural proteins. proteins. • All picornaviruses replicate in the cytoplasm.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)Hepatitis A Virus (HAV)

Hepatovirus and liver diseaseHepatovirus and liver disease

Acute, self-limiting liver disease

Fecal-oral transmission of HAVFecal-oral transmission of HAV

Hepatitis A Cases in Pennsylvania Rise to 510Hepatitis A Cases in Pennsylvania Rise to 510 Pittsburgh Blog Pittsburgh Blog

« Green Onions Pulled From Chi-Chi's Menu Nationwide | | Main | | Pittsburgh Holiday Happenings »

November 17, 2003November 17, 2003 Hepatitis A Cases in Pennsylvania Rise to 510Hepatitis A Cases in Pennsylvania Rise to 510

The number of confirmed Hepatis A cases in Western Pennsylvania The number of confirmed Hepatis A cases in Western Pennsylvania have exceeded 500, including 3 deaths, in what has now become the have exceeded 500, including 3 deaths, in what has now become the largest hepatitis A outbreak in U.S. history, according to the Centers largest hepatitis A outbreak in U.S. history, according to the Centers for Disease Control and Prevention. As a precaution, many restaurant for Disease Control and Prevention. As a precaution, many restaurant chains are now removing green onions from their menus nationwide. chains are now removing green onions from their menus nationwide.

640 confirmed cases and 4 deaths640 confirmed cases and 4 deaths Traced back to onions from Mexico served in mild salsa during mid-Traced back to onions from Mexico served in mild salsa during mid-

OctoberOctober

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

General Features of Hepatitis A Infection

HAV time courseHAV time course

Virus ingestedVirus ingested Primary replication in Primary replication in

intestinal lining?intestinal lining? ViremiaViremia Virus sheddingVirus shedding Involvement of liverInvolvement of liver Elevated enzyme Elevated enzyme

profileprofile Immune responseImmune response

Use of Molecular Epidemiology to Confirm a Multistate Outbreak of Hepatitis A Caused by Consumption of Oysters

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.

Good ways to catch HAV

The enterovirus formerly The enterovirus formerly known as poliovirusknown as poliovirus

Humans only natural hostHumans only natural host Long history in our speciesLong history in our species Water-borneWater-borne Usually causes mild disease-Usually causes mild disease-

often with no real symptomsoften with no real symptoms All enteroviruses are All enteroviruses are

neurotropicneurotropic

Disease progressionDisease progression IngestionIngestion Primary replication, lymph nodesPrimary replication, lymph nodes Primary viremiaPrimary viremia 95% asymptomatic95% asymptomatic Secondary viremia and further Secondary viremia and further

replication in other tissuesreplication in other tissues 4-5% mild symptoms4-5% mild symptoms Progression to CNSProgression to CNS Neurological symptoms-less than Neurological symptoms-less than

1%are1%are Paralytic cases even more rareParalytic cases even more rare Virus shedding in fecesVirus shedding in feces

A 20A 20thth Century Problem-Why? Century Problem-Why?

Important findings leading to the Control of Poliovirus1908 - 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 vaccineImpact of vaccine

Salk inactivated vaccine, injectable, 1955Salk inactivated vaccine, injectable, 1955 Sabin attenuated vaccine, oral, 1961-62Sabin attenuated vaccine, oral, 1961-62 OPV provides strong immunityOPV provides strong immunity ““attenuated” vaccineattenuated” vaccine

Eradication Initiative Begun 1988Eradication Initiative Begun 1988 WHO, UNICEF, CDC-goal: 2000WHO, UNICEF, CDC-goal: 2000 Rotary InternationalRotary International Private foundationsPrivate foundations Strategy includes:Strategy includes:

Childhood coverageChildhood coverage

National Immunization DaysNational Immunization Days

SurveillanceSurveillance

Follow upFollow up

MilestonesMilestones Western Hemisphere polio-free 1994Western Hemisphere polio-free 1994 Europe polio-free 2002Europe polio-free 2002 Pulse Polio campaign reduces cases in Pulse Polio campaign reduces cases in

India to 66 by 2005; 1979 worldwideIndia to 66 by 2005; 1979 worldwide India polio-free 2012India polio-free 2012 Endemic polio in 3 countries: Nigeria Endemic polio in 3 countries: Nigeria

Pakistan AfghanistanPakistan Afghanistan Scattered elsewhere-introducedScattered elsewhere-introduced

Learn in Business and Global Learn in Business and Global CitizenshipCitizenship

February 11, 2013 at 1:00 PM February 11, 2013 at 1:00 PM

Bill Gates Says Expect Polio Bill Gates Says Expect Polio Eradication by 2018, Measles Eradication by 2018, Measles

and Malaria, You're Nextand Malaria, You're Next

Norwalk and Norwalk-like viruses Norwalk and Norwalk-like viruses (Noroviruses) Caliciviridae(Noroviruses) Caliciviridae

School outbreak, Norwalk, School outbreak, Norwalk, Ohio, 1968Ohio, 1968

Acute gastroenteritisAcute gastroenteritis 50% of 232 students and 50% of 232 students and

teachers affectedteachers affected Secondary attack rate of Secondary attack rate of

32% among families32% among families Virus particles discovered Virus particles discovered

in stool filtrate, 1972in stool filtrate, 1972

Norovirus outbreaks reported on 2 cruise ships that sailed the CaribbeanBy Eliott C. McLaughlin, CNNupdated 4:50 PM EST, Fri January 31, 2014

Cruise passengers talk about Caribbean Princess trip that returned to Houston earlyFriday, January 31, 2014

Disney ship docks with 195 illNext week's cruise canceled to sanitize vesselSaturday, 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.