Picornaviruses ate.edu
Picornaviruses
3/27/13
Small, RNA viruses
+ strand RNA acts as mRNA
7400 bases
has poly A tail
VPg attached to 5'end
Genome-translated as one polypeptide
Viral protease self-excises then aids host proteases in cleavage
Replication-
Bind surface structures (ICAM1) is common
Genome injection into cytoplasm
Binds ribosome and alters to decrease translation of host mRNA
Members-
Enteroviruses-only found in humans but can reside in standing water -ponds are common
Coxsackieviruses A&B and poliovirus
Polio
More severe in adolescents than children
Attacks Anterior Horns of CNS
most infections are assymptomatic
Begins with mild symptoms
Paralytic polio 0.1-2% of infections
Vaccination very successful-some incidents of paralysis as a result of oral strain regaining virulence
Coxsackievirus A-
Herpangina-oral lesions of soft palate and uvula
Hand-foot & mouth disease-causes vascular lesions
Coxsackievirus B-
Pleurodynia-aggravation of outer membrane of lung
Myocardia-most severe in neonates
Rhinovirus-cannot survive stomach and intestinal tract
Usually limited to upper respiratory tract
Causes 60% of colds
Transmitted by aerosol or fomites
typically introduced to nasal epithelium
may also infect conjuctiva
Undergoes genetic drift so surface presentation always changing
Short term immunity-18-24 months
Over 100 serotypes exist anyway
+ strand RNA acts as mRNA
7400 bases
has poly A tail
VPg attached to 5'end
Icosahedral capsid-60 structural units comprising 240 polypeptides
One of the four polypeptides is not exposed to external environment
acts as pseudoscaffold
Deep cleft present at axis of 5-fold symmetry called canyon
Infection-
Canyon interacts with ICAM of host epithelium
ICAM usually facilitates adherence of leukocytes to endothelium
ICAM shaped like a Flintstone hand (one thumb and three fingers)
Leukocytes bind to the thumb, but rhinovirus cleft binds to fingers
Binding causes endocytosis
Genome-translated as one polypeptide
Viral protease self-excises then aids host proteases in cleavage
Host ribosomes are altered limiting translation of host transcripts
Replication takes place in cytoplasm-up to 400,000 copies of viral genome/cell
Viruses result in lysis of host cell
Immune response:
Most symptoms are a result from immune response
Infected cells increase expression of pro-inflammatory cytokines
Recruit leukocytes and increases ICAM on adjacent cells
Mast cells and basophils produce histamine
Results in increased mucus production (rhinorrhea)
Sialic acid in mucus interferes with virus/host binding
Virus swept away in mucus flow
Temp increases to above 33°C inhibiting viral replication
Damaged cells are extruded
Treatments-most only diminish histamine response and fever resulting in longer infection
New therapies in testing that bind to canyon and prevent viral binding
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