Chapter 14: Picornaviruses and other (+) RNA Flashcards
Poliovirus Capsid
30 nm in diameter
Icosahedral
60 identical subunits (protomers)
Canyon- contain anti-receptor
Each Protomer has 4 different proteins
VP1, VP2, VP3 at surface
VP4 buried beneath shell
Canyon
Surface depression
Poliovirus Genome
7.7 kb, (+) ssRNA-> act as mRNA upon infection
6 features
Genome Feature 1
No cap - so ribosome does not bind to 5’ end
Genome Feature 2
Viral Protein Genome linked covalently linked to 5’ end
2 functions:
“Primer” for both (+) and (-) RNA synthesis
“Packaging signal”: only RNA lnked to VPg will be packaged
Genome Feature 3
5’ UTR: untranslated region, long (743 nt) leader sequence
Contains Internal Ribosome Entry Site
Important for translation and virulence
Genome Feature 4
Single ORF: Encode a single “polyprotein”
All structural genes except VPg gene on left side of genome
non-structural genes plus VPg on right side of genome
Genome Feature 5
3' UTR: 50-100nt Important in (-) strand synthesis
Genome Feature 6
Poly A at 3’ end
Poliovirus Anti-receptor
Capsid proteins in canyon
Not surface protrusion
Hide from immune surveillance (canyon is too narrow for antibody to access)
Poliovirus Receptor
Glycoprotein CD 155 (immunoglobulin-like), on many cell types
Major conformational change -> lost VP4
Poliovirus Entry and Uncoating
Endocytosis
VPg-RNA released into cytoplasm
VPg removed by cell enzyme
Poliovirus Translation and post-translational modification
Ribosome binds IRES and moves to AUG
Initiation complex forms
Genome -> a polyprotein->autoproteolytical cleavage by viral proteases
Polyproteins
P1-> myristylated-> all capsid proteins
P2. P3 -> VPg, non-structural proteins
Transcription and Genome Replication
After translation
Occur on replication complex
Viral RdRp as the 1st nt onto VPg
Replicative intermediate
(+) RNA has 3 functions
mRNA for translation
Template fo (-)RNA synthesis
Genome for packaging
Poliovirus Assembly
P1->VP0, VP3, VP1->1 promoter-> 1 pentamer -> procapsid
VPg-RNA inserted
Maturation
VP0 cleaved -> VP2 + VP4
Total virion proteins = 4x5x12+1(VPg)
Poliovirus Exit
via cell lysis
Burst size: 10^5 virions/infected cell
Cytopathic effects
1 “re-program” events
inhibit host gene expression
Viral protease shutoff host translation
Protease 2A cleave cap-binding protein
Ribosome no longer recognize capped mRNA
No cellular mRNA translation
Viral translation still occurs
Viral proteins block vesicle traffic from ER to cis Golgi
Proteins 2B and 3A inhibit host protein secretion
More vesicles available for viral RNA replication on vesicle
Cytopathology and polio (poliomyelitis)
fecal-oral transmission Receptors only in human nasopharynx, gut, spinal cord most infections asymptomatic Disease is rare Infectious dose < 100 virions
Vaccines
Oral polio vaccine 1 dose Polio shot(IPV) 4 doses