Virology Chp 14

Poliovirus

What body system can polio infect, replicate within and damage?

The Central Nervous System

Polio can lead to paralytic poliomyelitis? What is paralytic poliomyelitis?

Irreversible paralysis caused by the poliovirus

Do most people have paralytic symptoms?

No, only 1% of people infected with polio will have such symptoms.

Poliovirus afflicted mainly children. How much percentage of infections were the children entirely asymptomatic?

72%

How many people worldwide are still living with polio-induced paralysis?

10-20 Million people worldwide

The first depiction of a polio victim was on an Egyptian stele in? What did it show?

1580-1350 B.C. It showed foot drop deformity, a condition that prevents dorsiflexion of the foot.

Who was the first English physician to document poliomyelitis in 1789?

Michael Underwood

The Early Years of Polio (1841; Late 19th Century, 1894; 1907)

Image here

What are the ecological factors thought to increase the incidence of polio? How?

Growth & urbanization of cities.

Larger population of susceptible individuals at one time, resulting in an epidemic.

What was the first breakthrough concerning etiology of polio in 1905?

Ivar Wickman shows polio was an infectious disease that could be transmitted from an asymptomatic individual.

What was the second breakthrough concerning etiology of polio in 1909?

Physicians Karl Landsteiner and Erwin Popper identified that polio has a viral origin.

How did Karl Landsteiner and Erwin Popper identify polio as having a viral origin?

Induced spinal cord lesions similar to those observed in humans by injecting a baboon and rhesus monkey with spinal cord suspension from a polio victim.

In 1916 a major polio epidemic happened in NYC that resulted in 9,000< cases of paralytic polio and 2k deaths in the city. What months did the epidemic peak? Why was it hard for scientists to figure out the mode of transmission?

During the summer months when people were out vacationing at beaches, going to movie theaters.

Scientists knew polio was caused by a virus but couldn’t figure out the mode of transmission due to the fact most people infected were asymptomatic.

Which researchers experiment suggested that the virus was transmitted orally? How was the experiment conducted?

Researchers Albert Sabin and Robert Ward analyzed tissues from fatal cases of polio which determined the primary infection occurred in the gastrointestinal tract.

Which scientists in received a Nobel prize in 1954 for their discovery in 1949? What was the discovery?

John Enders, Thomas Weller, and Frederick Robbins.

They discovered a method for growing poliovirus in a variety of human embryonic tissues using cell cultures.

Using the previous scientists’ method, John Salk in 1951 was able to what?

John Salk was about to propagate polio in monkey’s kidney cells.

Salk propagated one strain of each serotype of poliovirus for a vaccine, however who determined that three serotypes of polio exist?

Bodian & Morgan in 1949

What type of vaccine formulation did Salk use?

Inactivated poliovirus using formalin.

In 1954 the massive vaccine trial began in April that included 1.5 million children. What was the percentage in effectiveness in preventing Polio?

The vaccine was 80-90% effective in preventing polio

True or False:In 1995 activated polio vaccine was approved for use.

False, inactivated polio vaccine by Salk was approved for used in 1995.

What was the second vaccine to be approved for polio? Who was it by? How was it administered?

Oral polio vaccine (OPV). The creator was Albert Sabin. 

It was administered as a liquid dose that is swallowed or given on a sugar cube

How many poliovirus strains do the IPV and OPV vaccs contain? How effective are they at producing immunity?

Three poliovirus strains.

Very effective; can produce immunity after 3-4 doses.

Due to ease of use OPV replaced IPV, however OPV contains attenuated poliovirus that can revert back to a neurovirulent strain.. what kind of polio comes from this?

Vaccine-derived poliovirus (VDPV).

What does Vaccine-derived poliovirus (VDPV) cause? Rarity? When does it occur?

Vaccine-associated paralytic polio (VAPP).

Quite rare: 1 individual out of every 2.4 million doses of the vaccine.

If it happens, it occurs 4-30 days after receiving the OPV.

In the United States how many cases of VAPP are caused each year by VDPV?

8-10 cases.

What’s the order, family, genus, and species for Polio?

Order- Picornavirales

Family- Picornaviridae

Genus- Enterovirus

Species- Enterovirus C

What are the 3 polio serotypes?

Poliovirus type 1 (PV1)

Poliovirus type 2 (PV2)

Poliovirus type 3 (PV3)

True or false: All serotypes are capable of causing paralytic poliomyelitis?

True

Which polio serotype causes the most epidemics of paralytic poliomyelitis?

PV1. Poliovirus type 1.

Who are the known reservoirs for poliovirus?

Humans.

How is poliovirus transmitted?

Through the fecal-oral route.

Poliovirus morphology? Naked/Enveloped? Resistance to what? RNA?.

Naked, acid resistant.

Resistant to detergents and 70% alcohol.

Icosahedral. Small 30nm

+ssRNA genome of 7.5kb

How long can poliovirus be stable in fresh water or seawater at 16 C(60F)?

1-2 months.

Poliovirus can be recovered from saliva and throat swabs, what is this evidence for?

Evidence for oral-oral transmission that can occur via droplets or sharing fomites.

Infection is inapparent in how many infections?

72%.

An infected individual is most infectious from what time range? How is the polio virus shed?

An infectious individual is most infectious from 7-10 days before until 7-10 days after symptoms appear.

The virus is shed through stool for 3-6 weeks and is communicable even if the individual is asymptomatic. 

Where does the poliovirus replicate after infection?

Polio replicates in the oropharynx and gastrointestinal tract mucosa.

The virus gains entry into the tonsils and Peyer’s patches (in the small intestine). How long after infection does the virus spread to regional lymph nodes and causes a primary or minor viremia to occur?

3-6 days following infection.

About 24% of individuals exhibit non-specific symptoms that last 2-3 days, what are they? (5 symptoms)

Headache

Fever

Rash

Sore throat

Abortive poliomyelitis, which resolves completely

During minor viremia, if distal sites get infected then secondary (major) viremia occurs. What does the virus infect at this state? How?

The virus infects the CNS either from the bloodstream or by infection of a peripheral nerve.

What are the two forms of disease that can occur upon infection of the CNS?

Nonparalytic aseptic meningitis & paralytic poliomyelitis.

Nonparalytic aseptic meningitis: How many cases progress to this? What are the symptoms? (6) Do they resolve completely?

1-5% cases progress to nonparalytic aseptic meningitis.

Symptoms include:

Inflammation of the brain and spinal cord membranes

Fever

Headache

Back pain

Stiffness in neck, back and/or legs

Abnormal heightened sensations that occur as result of nerve damage

Yes, these symptoms resolve completely in most individuals.

Paralytic poliomyelitis is the most severe manifestation of poliovirus infection. How often does it occur in symptomatic individuals?

Occurs in <1% symptomatic individuals.

Paralytic symptoms appear as if the person is recovering from abortive infection, when do they appear following prodromal symptoms? What are some of the symptoms?

1-18 days following prodromal symptoms.
Symptoms include:

Can occur absence of typical prodromal symptoms

Fever & headache accompany muscle pain and back/llimb spasms

Paralytic progresses within 2-4 days to a cute flaccid paralysis. What do these symptoms include?

Weakness of muscles

Reduced or absent of reflexes from the result of destruction of motor neurons

When neurons are damaged, control of the muscle response supplied by those nerves is reduced or lost.. Is paralysis symmetrical? When does it occur following infection?

Paralysis in asymmetrical and more common in the legs than in the arms.

Occurs 7-21 days following infection.

Muscle atrophy accompanies prolonged paralysis.

Paralytic poliomyelitis is classified into three types. What are they?

Spinal poliomyelitis.

Bulbar poliomyelitis.

Bulbospinal poliomyelitis.

What is Spinal poliomyelitis?

Infection of the anterior horn cells that affect the motor neurons of the body. Most common in legs but also can affect the back or neck. (79%)

What is Bulbar poliomyelitis?

Occurs when destruction of the bublar region of the brain stem happens, that controls autonomic functions such as swallowing and breathing (2%)

What is Bulbospinal poliomyelitis?

Affects both bulbar and spinal neurons (17%).

How many people with paralytic poliomyelitis recover completely? How many individuals have some degree of permanent paralysis?

10% of people will recover completely while 80% will have some degree of permanent paralysis.

How many people succumb to paralytic poliomyelitis infection?

5-10% of people succumb to the infection with 25-75% of cases involving bulbar involvement.

What are the fatality rates of paralytic poliomyelitis within adults and children? (Percentage)

15-30% fatality rates in adults.

2-5% fatality rates in children.

What’s the iron lung?

An artificial respirator that was invented to assist breathing in cases with respiratory involvement.

25-40$ of people who recover from paralytic polio experience post-polio syndrome (PPS), when does this occur? Is the virus present? What are the symptoms? Is it life threatening?

Occurs 15-40 years after the initial infection.

Virus will no longer be present.

Symptoms will include:

1. Muscle weakness

2. Fatgiue

3. Atrophy

Rarely life-threatening.

Poliovirus replication:

Infectious +ssRNA genome is translated immediately upon entry.

Poliovirus replication:

slide 33 here

Poliovirus replication: Attachment, Penetration, and Uncoating. The Polio capsid is composed of 60 copies of each 4 repeating proteins, what are they?

VP1, VP2, VP3, & VP4.

What’s the cell surface receptor for all three poliovirus serotypes?

CD155, also known as poliovirus receptor (PVR).

How was the proven that CD155 is the receptor used by poliovirus to enter cells?

Through transgenic mice.

Poliovirus translation & replication:

Poliovirus translation & replication:

Poliovirus translation & replication: Function of poliovirus proteins

Picture here

Poliovirus translation & replication:

Poliovirus translation & replication:

Poliovirus replication (assembly, maturation & release):

Virion undergoes maturation as VP0 is cleaved into VP2 and VP4 by host protease.

Released through lysis or release of vesicles involved in autophagy.

Poliovirus replication (assembly, maturation & release):

Why is polio a good target for eradication? (5)

1. Exclusively infects humans

2. Limited number of serotypes (3)

3. Virus does not cause persistent infection

4. Immunity appears lifelong

5. OPV is easy to administer 

Why is polio not an ideal target for eradication? (2)

1. Vast majority of infections are asymptomatic. (All children must be vaccinated; not just those that were in contact with an infected individual)

2. For full immunity, 4 does of the vac must be administered.

The Global Polio Eradication Initiative focus on? (4)

1. High route of immunization coverage

2. Supplementary immunization through National Immunization Days

3. Effective surveillance

4. Door-to-door immunization campaigns to immunize the last of the unvaccinated in a particular area.

What happen in 1988, the year the Global Polio Eradication Initiative was announced?

There were 350,000 annual cases.

1,00 children were paralyzed each day

Endemic in 125 countries

What countries were recently removed from the list of having polio?

India was removed in 2011. Nigeria in 2012.

What are the counties that still have polio?

Pakistan & Afghanistan.

Recent challenges of polio eradication efforts? (3)

1. Importation of polio into polio-free countries.

2. Political unrest, poor health infrastructures, and opposition from militant groups.

3. Choice of OPV has led to circulating VDPV strains.

When was the last case of paralytic poliomyelitis reported in the United States? Where was it imported from?

Last case of paralytic poliomyelitis in 1979, imported from Netherlands into unvaccinated Amish communities.