polio and other non-enveloped viruses Flashcards
non-enveloped RNA viruses (list)
rhinoviruses enteroviruses (enter through GI tract, but do not cause GI disease) apthoviruses Rotaviruses Calcivirus adenovirus
What are the viral gastroenteritis-causing viruses?
reoviruses (rotavirus)
caliciviruses (Norwalk virus)
adenovirus
astrovirus
rhinoviruses
enter upper respiratory tract, where infection is usually limited
major factor in asthma exacerbations
replication in oropharynx mucosal surfaces
frequent cause of common cold
many antigenic types (>100)
highly labile at low pH (therefore not actually enteroviruses)
also grow well at low temperature - allows for them to grow well in our noses/upper respiratory tract
biology similar to that of polio
aerosol spread so very infectious
picornaviruses (types)
enteroviruses polio coxsackie coxsackie A coxsackie B ECHO other enteroviruses rhinoviruses hepatovirus hepA
enteroviruses
enter oropharyngeal or intestinal mucosa secretory IgA can prevent infection spread by viremia to target tissues serum antibody blocks spread virus shed in feces high asymptomatic infection rate
replication and spread of enteroviruses What happens when skin becomes infected? Which picornavirus effect the muscle? Which picornavirus affect the brain? Which picornavirus affect the meninges?
replication in oropharynx and intestine mucosal surfaces - moves to lymph node then to blood then to skin, muscle, brain or meninges
in skin: causes hand-foot-and-mouth disease => rash, herpangina
in muscle: echoviruses and coxsackie viruses affect here - in heart causes myocarditis, pericarditis; in thorax causes pleurodynia
in brain: poliovirus and coxsackie A and B act here - cause paralytic disease and encephalitis
in meninges: Echovirus, poliovirus, and coxsackie A and B act here - cause meningitis
polio structure
each of VP1, 2, and 3 fold to form a beta barrel jelly roll
proteins interact to form hollow caspid with surface plateaus and canyons
the canyons contain the CD155 receptor binding sites
What are the mutation rates and species specificity of DNA viruses?
low mutation rate
species specific
What are the mutation rates RNA viruses?
how does this effect their interspecies infection rates?
How does this effect antivaccination efforts?
high mutation rate
allows them to cross species barrier
also creates challenges for vaccine/antiviral strategies
replication strategies of viruses are dictated by:
genome of incoming virus
absence of envelope (enteroviruses)
permissively of cell: availability of receptors and ability to overcome innate cellular defenses
how does the poliovirus prevent growth of host cells?
the viral protease kills CAP-binding protein
also, IRES (see next slide)
IRES
region of secondary structure upstream of coding region in host DNA
it’s non-coding - affects efficiency of translation
normally the efficiency of translation decreases as the translation machinery moves along the mRNA
if polio is present, nothing before IRES is translated but every thing after it is translated with high efficiency
polio has a IRES segment in its own genome - this allows it to shut off the translation of host cell proteins without affecting (or even while increasing) the translation of its own proteins
explanation from bharat: “IRES allow ribosome to translate a protein from a polycistronic mRNA. Without IRES the entire mRNA is made and the first protein or the first few proteins encoded on the mRNA are made more often than the other ones that come later due to ribosomal slipping, etc. The IRES experiment [when polio virus was added to cells and shut off translation of genes before the IRES] just showed that IRES are used to synthesize protein within the polycistronic mRNA. It also shows that the efficiency of protein synthesis due to IRES is specific to the translation machinery directed by viral proteins. In short, this proved that IRES are specific to a virus and that viral proteins manipulate host translation machinery to get proteins from a polycistronic mRNA.”
polio pathogenesis
- encounter - entry - spread - multiplication site - type of damage to host - prognosis? What percentage are asymptomatic? How does death insue?
encounter: fecal contamination
entry: oral
spread: viremia
multiplication: CNS
damage: attacks motor neurons in anterior horns of spinal cord and brain stem
outcome: 99% asymptomatic, causes death by paralysis of the intercostal muscles and diaphragm
polio pathogenesis timeline
day 0: invasion and multiplication in small intesitine
day 1: multiplicaiton in mesenteric lymph nodes
day 2: primary viremia
day 3: central focus of replication
day 5: initial appearance of antibody
day 6: CNS - invasion, multiplication, spread
day 10: high levels of antibody in serum
day 11: paralysis
day 12: excretion in feces
clinical aspects of polio… for mild infection? for paralytic infection?
most infection is subclinical or mild - fever, stiff neck, may see aseptic meningitis
paralytic polio has two types:
spinal destroys spinal motor neurons
bulbar destroy respiratory centers
types of antibody-mediated immunity (3)
1: active - due to infection or immunization (long-term, strong)
2: passive - due to maternal antibody usually (short-lived)
3: passive then active - infection during period of passive immunity (usually just after birth when maternal antibodies still present) - results in mild disease, resulting in active immunity
killed versus live vaccines for polio (Salk v Sabin)
Compare and contrast the Salk vs Sabin vaccines.
Which require boosters?
Which induces IgG and/or IgA?
Which vaccine is communicable to other people? What are the clinical repercussions of transmission?
killed vaccine (salk) requires boosters but is very safe and stable, injected so induces IgG - in US vaccine is 4 doses of this because there’s low risk worldwide so this is sufficient and safer
live vaccine (sabin) doesn’t require boosters and so gives long-term immunity but not safe for pregnant and immunodeficient individuals, especially since it can spread to the unvaccinated and revert to virulence. labile stability - orally administered - induces IgA and IgG - people who have been vaccinated with this don’t shed if infected (gives herd immunity) (but they do shed the vaccine, which is why it can put people who are immunodeficient or unvaccinated at risk if the virus in the vaccine reverts to its virulent state)
only side effect of vaccines is that they put those who are not vaccinated at risk
What are the symptoms of post-polio syndrome? Who is affected?
affects polio survivors who had an initial acute attack years before
get gradual weakening of muscles that were previously infected
also fatigue, muscle atrophy, pain from joint degeneration and skeletal deformities (such as scoliosis) common
respiratory muscles can weaken resulting in difficulty breathing
What is the replication cycle of coxsackie viruses?
How are they transmitted?
Are they stable in outside of a host?
Is antiviral therapy or vaccine available?
How is Coxsackie diagnosed?
replication cycle similar to that of polio
fecal oral transmission
classified into two groups, subdivided into A1 to A23 and B1 to B6
stable in environment - big problem in daycare
no antiviral therapy or vaccine
diagnose by isolation/cell culture, rising antibody titers, PCR for RNA in CSF, especially in the case of aspetic meningitis
What tissues does coxsackie virus group A target?
What are its symptoms?
tropism for skin and mucous membranes herpangina (fever, sore throat, pharygeal lesions) hand foot and mouth disease aseptic meningitis paralytic disease (rare)
What tissues does coxsackie virus group B affect?
What are its symptoms?
viscerotropism - targets intercostals
pleurodynia (severe unilateral pain in lower chest)
myocarditis (adult and neonatal - fever, chest pain, sign of congestive failure)
asceptic meningitis
paralytic disease (rare)
ECHO viruses
stands for enteric cytopathic human orphan viruses
replication cycle similar to that of polio
fecal-oral transmission, large number in feces
stable in environment, big problem in daycare
32 serotypes to date
cause rash, leading cause of aseptic meningitis
no vaccine or antivirals
What illness does enterovirus 70 cause?
causes acute hemorrhagic conjunctivitis
What illnesses does enterovirus 71 cause?
can cause HFMD, CNS infections
