picornaviruses Flashcards
picornavirus structure
nonenveloped, icosahedral positive sense ssRNA
List the viruses of the picornavirus group and dz they cause
PEERCH: poliovirus, echovirus (aseptic meningitis, hepatitis), enterovirus (respiratory), rhinovirus (cold), coxsackivirus (hand, foot and mouth dz, aseptic meningitis, myocarditis, pericarditis, herpangina), hepatitis A virus.
members of the enterovirus genus
enterovirus is a genus of the picornavirus family. It includes polio, coxsackie, echovirus, enterovirus
What molecules of the virus and the host define picornavirus serotypes?
Neutralizing antibodies from the host and antigenic epitopes of capsid proteins (on the surface of virus particles)
What is the Most Common Respiratory Virus Causing Infection among Patients of All Ages Hospitalized with Acute Respiratory Illness
picornaviruses- cause 25%
enterovirus 68
Most common enterovirus infection in the US in 2014. Causes mild to severe respiratory infections and in rare casses is associated with acute flaccid myelitis/ paralysis and brainstem/ grey matter spinal cord lesions
seasonal incidence of enterovirus
peaks in late summer August-September
Sx of aseptic meningitis
Acute onset of fever, chills, headache, photophobia, and pain on eye movement. Nausea and vomiting are also common. Headaches commonly persist for several days. Patients often describe the headaches as the worst they have ever experienced. Examination reveals meningismus without localizing neurologic signs. CT scans, when performed, are unremarkable
list causes of meningitis in newborn (0-6mos)
Group B strep, e coli, listeria
list causes of meningitis in children (6mos-6years)
S. pneumoniae, N. meningitidis, H flu type B, enterovirus
list causes of meningitis in 6-60yrs
N. meningitidis, enterovirus, S. pneumonia, HSV
list causes of meningitis in 60+ year olds
S. pneumoniae, gram negative rods, listeria
List causes of meningitis in HIV
cryptococcus, CMV, toxoplasmosis, JC virus
compare CSF findings in bacterial, viral and fungal meningitis
bacterial: increased pressure, PMNs, increased protein, decreased sugar. Viral: nl/ elevated pressure, lymphocytes, nl protein and nl sugar. Fungal: increased pressure, lymphocytes, increased protein, decreased sugar
Which picornavirus is associated with myocarditis
coxsackivirus B- occurs in newborns, adolescent or young adults. 10% progress to chronic dilated cardiomyopathy
Hand foot and mouth disease
young children with with fever, anorexia, and malaise followed by the development of sore throat and vesicles on the hands, feet and mouth. Highly contagious. Usually caused by coxsackievirus A16 or enterovirus 71
Picornavirus associated with hemorrhagic conjunctivitis
enterovirus 70 and coxsackievirus A24.
picornavirus penetration into host
Pentamer Extrusion Model: The genomic RNA is extruded from the virion particle into the host cell cytoplasm; through the cell membrane
picornavirus RNA replication
occurs in cytoplasm. Positive sense ssRNA is copied into negative strand RNA by RNA-dependent RNA polymerase, forming a dsRNA intermediate called a replicative intermediate. Negative strand RNA is then copied to make more positive strand RNA.
does picornavirus have replication proteins
NO- virion particles do not contain replicase (RNA dependent RNA polymerase, RNA helicase, capping enzymes)
picornavirus transcription/ translation
the positive sense RNA is used directly as mRNA for translation
picornavirus protein synthesis
After translation of a single polypeptide, it is cleaved into functional viral proteins by viral proteases. Proteins include VP1-4, 2Apro (protease), 3Cpro (protease). Occurs in cytoplasm
Why are most picornavirus infections innocuous
the patient’s acquired immune response typically produces serotype-specific neutralizing antibodies before the virus spreads from mucosal portals of entry to critical target organs
picornavirus pathogenesis
Infection at mucosal surface > viremia to lymph nodes and peripheral tissues > Interferon production limits initial viral replication > secondary viremia (5-15 days later) spreads virus to target organs > IgM and IgG neutralize virus
functions of IgG vs IgA in picornavirus infection
IgG blocks viremia and disease, but not infection b/c it is not at mucosal surfaces. IgA blocks infection at mucosal surfaces
Poliovirus clinical outcomes
Inapparent infection (95%), Minor URI/ gastroenteritis (constipation more common than diarrhea), aseptic meningitis, paralytic poliomyelitis (acute flaccid paralysis)
poliovirus pathogenesis
ingest fecal material > primary replication in pharynx, small intestine and lymph nodes > viremia to non-neural tissue (day 1-2) > amplified viremia (day 2-7) > CNS infection across BBB or retrograde axonal infection from motor neurons resulting in killed motor neurons (day 7-14)
bulbar polio
poliovirus attacks the motor neurons of the brain stem - reducing breathing capacity and causing difficulty in swallowing and speaking
how long is polio virus shed
fecal shedding for 2-6 weeks
polio immunity
Neutralizing antibodies bind nucleocapsid, interfering with attachment and uncoating. Natural, life-long immunity occurs following infections (most often subclinical infections).
Maternal antibodies can protect newborns for 6-8 weeks. Humoral immunity does not prevent GI infection, i.e., no sterilizing immunityNeutralizing antibodies bind nucleocapsid, interfering with attachment and uncoating. Natural, life-long immunity occurs following infections (most often subclinical infections).
Maternal antibodies can protect newborns for 6-8 weeks. Humoral immunity does not prevent GI infection, i.e., no sterilizing immunity
inactivated poliovirus vaccine- what is it, advantages and disadvantages
trivalent against all 3 serotypes. Killed virus. Advantages: systemic IgM/IgG immunity, no live virus, acceptable for immunocompromised. Disadvantages: cost, injection, poor mucosal immunity
oral poliovirus vaccine- what is it, advantages/ disadvantages
Trivalent Live attenuated virus given orally. Advantages: Induces mucosal immunity (IgA) and systemic IgM/IgG, Ease of administration (oral),Inexpensive. Disadvantages: attenuated virus commonly reverts to virulent forms in vacinnees, revertant virus passes in stool and infects contacts
which poliovirus vaccine is currently recommended
As of 2000, the CDC recommends exclusive use of Inactivated poliovirus in US- IPV given at 2, 4, and 12 months
how many mutations occur for oral poliovirus vaccine to cause vaccine associated paralytic poliomyelitis
6 mutations for poliovirus 1, 2-3 for poliovirus 2, and 2-3 for poliovirus 3
who gets vaccine associated paralytic poliomyelitis
- OPV Vaccine Recipients (Infants, First Dose). 2. Contacts of OPV Recipients (Non-immune, First Exposure). 3. Immunocompromised (Recipients and Contacts)
What is the second human disease set to be eradicated
Guinea worm disease- a parasite acquired from drinking water
bivalent oral polio vaccine
has better protection against poio types 1 and 3 than the trivalent OPV. But, it does not provide protection against serotype 2
Which serotypes of polio have been eradicated
Wildtype 2 in 1999. Wildtype 3 in 2013
Which viruses can cause acute flaccid paralysis
coxsackie A and B viruses, enterovirus 71, echovirus, polio
Who gets persistent infections by OPV
people with B cell immunodeficiencies like X-linked agammaglobulinemia and CVID. Without neutralizing Abs, the OPV is persistently shed from feces
which serotypes of oral polio vaccine can revert to produce circulating vaccine-derive poliovirus
OPV serotypes 1, 2, and 3. And all of these are capable of causing outbreaks of acute flaccid paralysis
