Chapter 5 - Picornaviruses part 1 Flashcards
Should we be concerned about poliovirus
Most are vaccinated in Canada, but international travel is common and easy for someone to travel to an area where polio is an endemic and come back to infect people
Endemic = virus has a continued presence in the community, usual.y a few case throughout the year
History of Poliovirus Infections
Improvement in sanitation increased in incidence of polio infections
Because polio virus can only replicate in human and spread from human to human
By being cleaner, less immunity cuz not exposed (hypothesis)
Poliomyelitis
Inflammation of the Grey matter of spinal cord
Caused by virus which can infect many types of cells in human and result acute infection
- any cells with CD155 can be infected
Most cases (>95%) are limited to the throat and GI epithelial cells
Only small number of cases did the virus penetrate the CNS causing major illness
- When the virus infects CNS it made a mistake
- no benefit for virus infecting CNS, it cannot be transmitted to another person
- Virus can spread
Infection route and types of polio
Abortive:
- Ingestion of poliovirus in food/water
- infection of epithelial cells of throat and intestine
- Replication of virus
Result in Abortive Polio (95% of cases)
The virus also excreted in feces
Rarely during replication, it can spread to the bloodstream
If involve CNS becomes paralytic polio (0.1-0.5%),
if doesn’t involve CNS becomes nonparalytic polio (1-2%)
Paralytic
Infection of motor neurons of the spinal cord, brain stem, or motor cortex
Non Paralyrtic
Local inflammatory response, self-limiting infection of meninges
Abortive Polio
Many cases are asymptomatic
Other cases present as mild cold for about 72 hours
- Slight fever, sore throat, headache
Accounts for 95% of infections
Most cases are undiagnosed at the time of infection
Non Paralytic polio
Present with mild influenza like symptoms
Back pain, muscle stiffness and tenderness,
Headache moderate fever
Excessive fatigue, irritability
Vomiting diarrhea, skin lesion
Symptoms last 1-2 weeks
Accounts for 1-2% of infection
Paralytic polio
Fever for 5-6 days before other symptoms
Other symptoms develop fast
Abnormal sensation in an area
Muscle cramps or spasm in calf neck or back, stiff neck and back headaches
Muscle pain and weakness that is only one-sided
- Location depends on where spinal cord is infected
- Worsens into paralysis
Sensitivity to touch, mild touch may be painful
Difficult breathing if respiratory muscle involved
In very severe cases: death if breathing muscle paralyzed
Not too severe:
- paralysis of the muscle
- intense physiotherapy can regain some use of a limb
- loss of surviving motor neurons with age
- can lead to post-polio syndrome
Post polio syndrome (PPS)
PPS develops 30-40 years after initial polio illness
Symptoms include
- New muscle weakness: common in muscle thazt had a nerve damage from polio
- fatigue
- muscle joint pain
- Muscle affected by polio tend to be weaker than normal other muscles having to work harder putting extra wear and tear on the muscle
PPS progresses slowly
What causes PPS
PPS isn’t caused by reactivation of the virus
- Poliovirus causes an acute infection
- As an RNA virus, it cannot persist in the cell for decades
- no evidence of poliovirus circulating in North America
Caused by:
- surviving motor neurons may sprout new dendrites to promote use of these muscle
Over the years, this stress may be more than the neuron can handle
The dendrites deteriorate and eventually so does the neuron itself
Who does poliovirus affect
Mainly affect children under age of 5
- These children may not have been exposed to virus developed immunity
However older children teenagers and even adults can be infected and suffer the effects of polio
If you have not been vaccinated you are at risk especially if travel to endemic areas
As you get older, you are more likely to get paralysis polio and the effects of it also get more severe
- In children if infect CNS, just get non paralytic polio
Who does poliovirus affect
Several key factors have been identified as increasing likelihood of paralysis
- Pregnancy
- Removal of tonsils
- Immune deficient
- Intramuscular injection
- Injury
- Strenuous exercise
Why do we study poliovirus
Simple replication path
Humans are the only known natural host
Poliovirus known to infect monkey kidney cell line
- This monkey cell line is used to manufacture polio vaccine
- Cell lines are not normal cells
Poliovirus is still a problem in many countries, but endemic in only Pakistan and Afghanistan
Why poliovirus is still a problem
Vaccine programs have lapsed
- virus has been re-introduced into a country where it had once been eradicated
Some areas may be geographically difficult to reach
Political unrest with military actions
Local populations refusing vaccination - distrust of western societies
Until the virus is eradicated globally, it is a problem for all countries in the world
Just because it is currently circulating in North America does not mean that it cannot return –especially if the number of individuals that are not vaccinated continues to increase
Generation of Polio Vaccines
Infected human cells
- -> wild poliovirus
- -> Passage through monkey cell line
- monkey cell line must have a structure that virus can bind to - might not be as effective as human cells but enough to initiate genome entry
- -> Mutations
- -> Reduced virulence to human cell line (attenuated)
- ->–>
1. prepare as oral vaccine or
2. chemically inactive –> prepare as injected vaccine
Polio Vaccine - I
Infect human cell like with wild type poliovirus
–>propagate poliovirus, will find mostly wild type progeny but there will be mutants
~ 1 in 10 viruses progeny will produce a single mutation in the genome
Mutation may be neutral.
If harmful it may no longer be replicated
Or good mutation - strain can infect different species of host cell
Polio Vaccine - II
Take those virus progeny (along with mutated ones) and infect monkey cell line
–> propagate polio virus
–> Mutant viruses are able to infect and replicate the non-human cell line,
the wild type strain does not infect and replicate as well
- the mutated viruses are selected for further propagation
aka now mutated virus more fit to monkey cell line aka _attenuated for human cell line
Polio Vaccine - III
Using those mutated polio virus only infected monkey cell line
–> propagate poliovirus
–> Possible that some virus mutated back to wild-type (virument ) form - a potential problem in OPV
antibody against the mutated virus should bind to wild type virus
Repeat the passage of polioviruses on the non-human cell line several times
- This allows for the mutate viruses to acquire additional mutations that allow them to replicate well in the non-human cell line
- the wild type viruses are diluted out of existence cell culture
Polio vaccine
The virus strain has accumulated many mutations relative to the original wild stain
- it may not loner be able to infect human cell line
- it may be able to infect human cell, but not replicate as well within it
Now we made attenuated virus may be used as vaccine.
However some virus particles may revert and mutate back to wild type regaining ability to infect humans cell well
Salks’s Vaccine - Injected Poliovaccine
IPV:
virus is inactivation, no viral replication, cannot spread to other susceptible people
The virus is injected into muscle (booster vaccine)
- get humoral response
- IgG immunity in blood
- but not gut immunity, could still get infection in gut
- could spread to other susceptible people
- no concern if virus enter blood stream
Sabin’s Vaccine - Injected Poliovaccine
OPV
virus can replicate in throat or gut:
- might spread to bloodstream (viremia)- systemic immunity (IgG in bool –> immunity)
- or if infection of motor neurons –> paralytic polio - Local immunity - IgA secretion in gut –> immunity
- Excretion from body
- contamination of food and water
- possibly infect other susceptible people
