Polio

Picornaviridae

What is the virus family of poliovirus?

Among the smallest of all ssRNA+ viruses, only 22-30 nm icosahedral virions

What is Picornaviridae like?

Via fecal-oral route (enterovirus)

How does the poliovirus enter the human body?

Replicates in cells of small intestine and lymph nodes (that drain intestines) and virus is shed in feces for several weeks

What does poliovirus do once it is in the human body?

In about 1 in 200 cases (around 0.5% of cases; paralysis is actually rare)

How often does the virulent virus affect motor neurons of CNS and PNS?

In the summer months the cause mysterious at first

When did paralytic polio epidemics occur in America>

Highly variable (mild to severe- swallowing and breathing impaired)

What are patterns of paralysis like in polio?

- Over 57,000 deaths

- Over 3000 deaths

What were the numbers of polio like in Summer of 1952 (peak)?

5-9 year olds

When was the peak incidence of polio in summer 1952?

1st world (sanitation created epidemics)

Polio epidemics are a disease of the ______________________

Endemic

______________ in the third world

nervous system, digestive tract, neurovirulence

Few people recognize that polio is NOT primarily a virus of the _______________, but the _______________. It has a low incidence of __________________, but this is such a devastating consequence that it gets our attention

grew; summer 1952; endemic

Polio epidemics _____________ with each decade of the 20th century. The _____________________ was the peak year of summer polio epidemics. Strangely, polio was ____________ in poor parts of the world

Iron lungs

What were used to keep people alive when their diaphragm was paralyzed and they could not breathe for themselves?

Had diesel powered generator that had to kick in when power was out; could also turn pull and push a lever on the iron lung

What happens when the power went out to iron lungs?

Pneumonia, bedsores, and blood infections (so pattern would repeat again next semester and people would fill the leftover iron lungs)

Why did most people in an iron lung die in a year?

Salk vaccine

What vaccine was tested in western PA?

polio pioneers

Perhaps your relatives in Pittsburgh and western PA were recruited as _____________________

Lined up at schools to have their children vaccinated, hoping they got the vaccine and not the placebo

What did parents do with their children when the Salk vaccine came out?

Killed virus vaccine (growing virus in cells, virus was killed)

What type of vaccine was the Salk vaccine?

University of Pittsburgh

Where did Jonas Salk work?

Polio pioneers

What were local Pittsburgh children called?

Foundation for Infantile Paralysis (March of Dimes)

What was Jonas Salk's vaccine supported by?

Polio rates plummet; "Patenting the Sun" book by Jane S. Smith

What happened after the Salk vaccine was produced?

Jonas was a bad businessman, we would pay anything for it but since he didn't patent the vaccine he would not make the fortune there for the taking; Salk responded that the vaccine belonged to everybody, it would be like patenting the sun

What did a reporter announce about Jonas Salk, and what was his response?

African green monkey kidney cells

The Salk vaccine was a killed vaccine where the polio virus was grown in what?

Millions of children

Who was the Salk vaccine effective for?

Boosters

What was necessary for the Salk vaccine?

A world fearful of polio

What did the Salk Vaccine transform?

Live (virus will reproduce), attenuated (weakened) vaccine, administered as a cherry flavored liquid

What kind of vaccine was the Sabin vaccine?

Stronger immune response, vaccine spread to non-immune family and community contacts (fecal oral route)

What were advantages of the Sabin vaccine?

Of the types of polio virus, 3rd type was genetically unstable. Reverted to neurovirulence (vaccine-associated polio, could cause paralytic polio)

What were problems of the Sabin vaccine?

oral, intestines, greater, life-long

Sabin was an _____ vaccine that infected the ____________ and induced a much _____________ immune response bc it's alive and __________________ immunity.

It could mutate to neurovirulence

What was the problem with the Sabin vaccine being a viable polio virus?

Only use Salk

Since 2000, what have we done?

SV-40 (simian virus-40)

What was a crisis that came from looking for viruses in monkeys?

The 1970's in African green monkeys (so would be in Salk and Sabin vaccines)

What was the SV-40 virus discovered in?

Can't grow virus (for Salk vaccine, for instance) without cells. You don't know if another virus is in those cells if you haven't even identified the virus yet

Why would the SV-40 be in Salk and Sabin vaccines?

Tumors in lab rodents

What does SV-40 (a DNA tumor virus) cause?

Primary human fibroblasts (makes cancer in a dish)

What does SV-40 immortalize?

Tested male foreskins; regularly they only grow to 50 cells, with this virus they grew a lot more

What did we test to find out about human fibroblasts?

Some lots of Sabin vaccine (a live attenuated vaccine)

What was the SV-40 found to be present in?

No

Were millions of Sabin vaccinated children destined to develop SV-40 induced cancers?

Did not show evidence of a cancer epidemic

What did careful monitoring of tumors show?

An RNA tumor virus

What was identified in the 1980s?

Foamy virus

What were the Sabin vaccine lots checked for?

You know they exist.... what viruses will be found next? You won't know until we look for them

You can only look for viruses once what?

Even identified the virus yet

You can't detect another virus in those cells if you haven't what?

Xenotransplantation

interspecies transplants may present opportunity for trans-species virus transmission; transplant organs or tissues from one organism to another

Source of HIV-resistant bone marrow stem cells (immune reconstitution)

What were baboons tried as?

Pigs

What are model organisms for transplants?

A sugar (alpha 1, 3-galactose); the antibodies in human blood are directed to attack alpha 1, 3-galactose, or "alpha gal" which is found in the tissues of all non-primate mammals. The transplanted animal organs often fail to survive for less than a few hours

What do we need to remove on pig cell surface and why?

'Knock-out' genetics

What created humanized pigs without sugar on pig cell surface?

Cloning pigs

What was necessary to keep humanized pigs from re-acquiring objectionable surface sugar?

On case-by-case basis, a so-called compassionate case exception

When was pig organ transplantation to humans allowed?

Over concern about Porcine endogenous retroviruses (PERVs); we don't know what viruses are in pigs and we don't want to unleash an epidemic of pig viruses in human population (fears that started with the SV-40 are still with us)

Why was routine xenotransplantation blocked by vocal virologists?

SV-40 (and other viruses) in Sabin vaccine

Lessons of what continued to reverberate?

Gene splicing CRISPR technology may have removed the objection of PERVs (removed all 23 PERVs from pig genome)

What happened in 2015 that allowed us to use 'humanized' pig organs?

Kidneys

41,354 Americans received a transplanted organ in 2021, more than half of them what?

Experimental pig kidney transplants

What was used in 2 brain dead human recipients?

A dozen

About how many Americans die each day waiting for an organ transplant?

humanized pig heart transplant

First ______________________ with FDA emergency authorization

3,800

____________ Americans received human heart transplants in 2021, limited by donor availability

He survived for 2 months, passing the critical rejection period, but then he died from a porcine CMV infection (herpes virus)

What happened to a 57 year old man that got a pig heart?

10 genetic modifications from Revivicor, a VA Regenerative medicine company

What did the donor pig heart carry?

In 2000, 2005, 2010, 2015, 2020, 2025

When did WHO targets for eradication fail?

Rotary International Funding

What is still key to success?

Nigeria, and Pakistan/Afghanistan border (tribal and lawless areas; polio vaccine workers are killed)

Where are there remaining endemic cases in?

Polio vaccine aid workers

_________________________ threatened and killed

Civil unrest, superstition, and ignorance

What remain barriers to eradication?