BIO315 Chapter 8: Poliovirus & Other Enteroviruses

What % of poliovirus infections cause a major illness, such as flaccid paralysis?

Less than 1%

poliovirus infects:

MOTOR NEURONS (not sensory)

In 1942, the Kenney Institute opened in:

Minneapolis

Dilated cardiomyopathy

disease of the <3 muscle that causes the <3 to become enlarged & to pump less strongly - the <3 becomes thin, weak, or floppy, & is unable to pump blood efficiently around the body causing fluid to build up in the lungs, which leads to congestion & the feeling of breathlessness. - this has been associated w/ certain Coxsackievirus infections

Serotype

groups w/in a species of virus that share distinctive surface structures, such as different antigens

poliovirus can be present in:

human feces for 3-6 weeks

Where do enteroviruses multiply?

in the mucosa of the gut

+ssRNA genome of poliovirus is

infectious

severe form of poliomyelitis:

inflammation & destruction of neurons in the gray matter of anterior horn of SC

serotype 2

least likely to cause paralysis

Peyer's patches

lymph nodes in walls of intestines near the junction of the ileum & colon

major viremia causes:

minor symptoms

Characteristic of Enteroviruses

most infections occur during childhood & tend to produce life-long immunity.

serotype 1

most likely to cause paralysis

infants

mostly those in diapers, the most efficient transmitters of infection

How are the ubiquitous pathogens of the enteroviruses transmitted?

person-to-person via an oral-fecal route

mouth

portal of entry for polioviruses

Autocleavage

process by which protease cleaves itself

vaccine-associated paralytic polio

rare occurrence of poliomyelitis in a person who received the OPV

polioviruses spread through:

regional lymph nodes to the blood

the 5' end of poliovirus genome forms a clover leaf or tRNA like structure that plays a key role in:

replicative process of RNA molecule

paralytic poliomyelitis

severe inflammation that can destroy motor nerves & resulting paralysis can be permanent

polioviruses replicate in:

the anterior horn cells of the SC

Rhinoviruses are restricted to replication in cells of

the respiratory tract

once poliovirus attaches to receptor:

the viral capsid enters host cell via ENDOCYTIC PATHWAY

~95% of all poliovirus infections are

asymptomatic

Bulbar Poliomyelitis

characterized by muscle weakness, impairing a persons ability to talk or swallow - eventually, lung muscles are paralyzed, requiring the need for an iron lung or respiratory to aid in breathing

chemical inactivation of enteroviruses is achieved via:

chlorine, HCl, aldehydes; heating at 122*F for 1 hr in absence of calcium & magnesium can inactivate enteroviruses

Bulbospinal Poliomyelitis

combination of bulbar & spinal paralysis

PPS

condition that affects polio survivors years after recovery from an initial acute infection by poliovirus - most common symptoms: muscle weakness & fatigue & muscle atrophy

WHAT PROPORTION NEEDS TO BE VACCINATED?

- % OF PEOPLE WHO NEED TO BE VACCINATED = 1 - GOAL R0 / EXISTING R0 IN CASE OF POLIO: 1 - (1/6) = 5/6 83% PEOPL E TO BE VACCINATED IN ORDER TO CONTROL THE INFECTION!

What is R0?

- R0 = # of new infections that can be caused by an existing infection. - Mainly in a susceptible population - What is minimal % of people in that area that need to be vaccinate.

OPV

- developed 1961 by Sabin - consists of mix of live, attenuated strains of all 3 virus serotypes - administered orally to infants 2-18 months of age w/ syrup, water, or milk or on cake, break, or a sugar cube

IPV

- developed in 1955 by Salk - consists of 3 killed strains of virus - given via intramuscular injection

Poliomyelitis

- infectious disease caused by enterovirus that's spread by oral-fecal route of transmission - in severe cases, symptoms may involve the weakening or paralysis of the muscles of the lungs & extremities of its victims - this is rare today because of vaccination efforts

Enterovirus Genome

- naked - ss+RNA genome packed w/in a small icosahedral capsid

What viruses make up the Picornaviridae family?

- polio - hep A - foot-and-mouth-disease virus

potential roadblocks to global eradication:

- poliovirus is contagious - IPV inefficient in preventing spread of virus - OPV us in tropical countries is problematic - tensions between those who favor mass vaccination & those who don't - verification of success is hard since poliovirus infections are NOT clinically obvious.

UTR

- section of viral or celluar mRNAs that's not translated by cellular ribosomes into protein - usually located at the 5' or 3' ends of viral mRNAs - may contain a hairpin structure at 5' end of a viral mRNA called the IRES

PVR

- transmembrane protein belonging to Ig superfamily of proteins - serves as a cellular receptor for poliovirus entry into host cells

In the US, a nationwide vaccination program using the Salk vaccine began in:

1955

How many types of enteroviruses have been determined to cause recognizable infectious diseases?

20

incubation period for poliomyelitis:

6-20 days; can range from 3-35 days

convalescent serum

Ab-rich serum obtained from a convalescing patient

After viral +ssRNA genome is 1st released into the cytoplasm of the cell it:

Acts as a messenger RNA

Enteroviruses can be inactivated by:

Aldehydes

Amantadine

An antiviral drug that blocks the M2 ion channel function of influenza A viruses, resulting in the incomplete release of the viral ribonuclear proteins through interference w/ the uncoating step of its replication cycle.

Which form of poliomyelitis results in the destruction of nerves involved in speaking, swallowing, and breathing, often necessitating use of an iron lung?

Bulbar - bulbar poliomyelitis causes muscle weakness, impairing a person's ability to talk or swallow. - Eventually it may cause paralysis of breathing, in which case an iron lung or respirator may be required - less common than spinal poliomyelitis.

What was the 1st enterovirus discovered AFTER poliovirus?

Coxsackie viruses

cDNA

DNA that's synthesized from viral RNA genome that acts as a template to copy the RNA into this - rxn is catalyzed by RT - RT is produced by all retroviruses, including HIV & hep B virus

infection with 1 serotype ___________ confer immunity against a different serotype.

DOES NOT

A mother brings her 3-year-old son to the family pediatrician. The child initially presents with a fever, headache, and neck pain. A few weeks later the child is admitted to the hospital due to severe difficulty breathing and unexplained paralysis of his left leg. Which of the following viruses is most likely to be the cause of this child's symptoms?

Enterovirus D68

As of 2015, countries in Arica & the Middle East were polio-free.

FALSE

Polio virus infection can be cured using anti-viral drugs.

FALSE

Poliovirus is one of the most thoroughly investigated viruses of all time, and its molecular mechanism of action is well known.

FALSE

Poliovirus isolation in culture is no longer used to diagnose poliomyelitis.

FALSE

Potential roadblock to global eradication was identified as the lack of an animal reservoir.

FALSE

The Salk Vaccine in rare cases can cause poliomyelitis, a situation termed vaccine-associated paralytic polio.

FALSE; OPV by Sabin

Gamma globulin was an effective early polio prophylactic.

FALSE; it was INEFFECTIVE

Only a small % of poliovirus infections are asymptomatic.

False; up to 95% are asymptomatic

most enteroviruses infect & replicated in the

GI tract

GOAL OF INFECTION IS TO:

HAVE R0 VALUE LESS THAN 1; TO STABILIZE OR ERADICATE!

Initiation of translation of the poliovirus poly-protein is dependent on which of the following?

IRES

What are hospital acquire infections?

NOSICOMIAL INFECTIONS

Due to low childhood vaccination rates and political unrest, _____________ remains one of the last remaining polio-endemic countries accounting for the majority of wild-type poliovirus infections.

Pakistan - accounts for 85% of all WT-poliovirus infections in 2014; this possess the continuous risk of spreading poliovirus infections as infected individuals move to other areas.

What family do the viruses of the Enterovirus genus belong to?

Picornaviridae family

Individuals who have recovered from paralytic polio can experience new muscle pain and weakness decades later due to:

Post-poliomyelitis syndrome (PPS)

What is the R0 for polio?

R0 < 1: - Existing: 00 - New: 0 - New/Existing : ½ = 0.5 <1 - When R0 is less than 1, the infection will not replicate any further & it can die out or be eradicated R0 = 1: - Existing: 00 - New: 00 - New/Existing 2/2=1 - When R0 value is 1, the infection can be stable For polio; R0 = 5 to 7: - R0 > 1 --> 00: 00000000: 8/2 = 4 - If greater than 1, it is an infection that is common to spread

Respiratory Enteroviruses

Rhinoviruses triggering asthma

The live, attenuated vaccine developed by Dr. Sabin included:

Serotypes 1, 2, 3

The polio virus is carried by the bloodstream to the:

Spinal Cord

At least 100 viruses w/in the Enterovirus genus are known to infect humans.

TRUE

Enteroviruses are transmitted from person to person by an oral-fecal route.

TRUE

Enteroviruses are transmitted from person to person via an oral-fecal route.

TRUE

In neutralization assays, Ab are added to a virus preparation.

TRUE

Nonhuman primates and humans are the sole natural hosts for the poliovirus.

TRUE

Polio viruses are naked and small.

TRUE

Post-poliomyelitis syndrome (PPS) occurs in a large portion of individuals who recover from paralytic poliomyelitis.

TRUE

Sister Elizabeth Kenney's new theory for treating paralysis emphasized "re-education" of muscles.

TRUE

The 1st step toward identifying host receptors involves the isolation of monoclonal Ab.

TRUE

T/F: Not all enteric viruses are enteroviruses.

TRUE!

Rhinoviruses are restricted to replication in cells of:

The respiratory tract

Flaccid paralysis

a loss of voluntary movt because weakness or loss of muscle tone tone has caused damage to nerves in the muscle (e.g., as a result of poliovirus infections)

Hand-foot-mouth disease

a virulent disease caused by enterovirus 71 & coxsackie viruses. - it's common in infants & children - symptoms: fever, sores in mouth, & blisters on the hands & bottoms of toes - self limiting, lasting 7-10 days

Spinal poliomyelitis

asymmetrical paralysis on one side of the body - the lower SC is infected by poliovirus, resulting in paralysis of the legs