CSB351Y1 Lecture Notes - Lecture 23: Cardiovirus, Myocarditis, Tissue Tropism
26 May 2018
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Lecture 23: Cardiovirus and Norovirus
Cardiovirus (similar to picornavirus)
• Oral-fecal, no specific illness, symptoms are acute myocarditis → sudden death possible
• Encodes factors that alter nuclear transport to suppress synthesis of antiviral factors, promote viral replication
• 67aa leader (L) – alters distribution of IFN regulatory proteins targeted to nucleus (suppress IFN production)
- IFN blocks viral infections (cytokines)
• Same long poly protein, proteolytically cleaved
Mengo virus – isolated from mosquitoes (can infect humans and primates), rates most affected, cows, pigs
- Acute fever in humans, no specific treatment (not severe enough to require vaccination)
- Ca suppess host’s iue espose eduig epessio of Nulea Fato kappa B usig ’ UTR
• Theile’s vius, ECMV ad Mego vius all have uiue AA L
- Theile’s Vius has aa leade potei otaiig zi-binding motif – inhibits IFN-a/B production by
infected cells and affects nucleo-cytoplasmic trafficking of host proteins
- Extra protein L* translated from alternative ORF
◼ Some ribosomes bind IRES at AUG of L or bypass to L* (2 different protective anti-IF proteins)
- Taslatio of vial polpotei ad L* depeds o IRES i ’ o odig egio
Theile’s vius Theile’s uie eephaloelitis virus (TMEV)
• Infections in CNS, causes inflammatory response with demyelination reminiscent of MS
- TMEV infected mice have mononuclear inflammatory response via virus specific CD4+ T cells targeting viru
(chronically persists in CNS)
Cardiovirus
• ’ UTL has poly C tract, next is secondary structure sequence(IRES) → polyprotein → cleavage to 3 large proteins
• Decline of protein synthesis after a few hours following infection – due to IRES (uncapped viral RNA)
outcompeting capped cellular mRNAs for initiation of translation (not virus-induced cleavage of p220 of cap
binding complex (eIF-4F)
Echoviruses
• Classification – echo (enteric cytopathogenic human orphan) members of enterovirus of picoviridae
• Host range – limited top rimates
• Transmission and tissue tropism – humans only reservoir, replication in oropharynx (throat) → stomach →
lower intestinal tract
- Oral fecal route (food, inoculation, blood, fetus vertical transmission)
• Pathogenicity – ifetios ae suliial do’t ause liial ifetio ut can cause diseases
Calciviridae (chalice like)
• Non enveloped, similar to picornavirus and togavirus but distinctive (different group), infects animals
• Norwalk/norovirus – causes gastroenteritis in humans, stomach flu (cruise ship disease), food borne disease
• Symptoms show after 1-3days of exposure and persist weeks
• Norwalk virus 23nm (empty virus particle to decoy immune system) and 38nm (no encapsidation, no lipid, small)
• Encodes 3 ORF – 1st (2C helicase, 3C cysteine protease, 3D RdRP = non-structural), 2nd (conserved AA motif of
PPG for self assembly into virus like particles), 3rd futio ot eluidated, seuee do’t ath othe potei
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Document Summary
Ifn blocks viral infections (cytokines: same long poly protein, proteolytically cleaved. Mengo virus isolated from mosquitoes (can infect humans and primates), rates most affected, cows, pigs. Acute fever in humans, no specific treatment (not severe enough to require vaccination) Ca(cid:374) supp(cid:396)ess host"s i(cid:373)(cid:373)u(cid:374)e (cid:396)espo(cid:374)se (cid:271)(cid:455) (cid:396)edu(cid:272)i(cid:374)g e(cid:454)p(cid:396)essio(cid:374) of nu(cid:272)lea(cid:396) fa(cid:272)to(cid:396) kappa b usi(cid:374)g (cid:1009)" utr: theile(cid:396)"s vi(cid:396)us, ecmv a(cid:374)d me(cid:374)go vi(cid:396)us all have u(cid:374)i(cid:395)ue (cid:1010)(cid:1011)aa l. Theile(cid:396)"s vi(cid:396)us has (cid:1011)(cid:1010)aa leade(cid:396) p(cid:396)otei(cid:374) (cid:272)o(cid:374)tai(cid:374)i(cid:374)g zi(cid:374)(cid:272)-binding motif inhibits ifn-a/b production by infected cells and affects nucleo-cytoplasmic trafficking of host proteins. Some ribosomes bind ires at aug of l or bypass to l* (2 different protective anti-if proteins) T(cid:396)a(cid:374)slatio(cid:374) of vi(cid:396)al pol(cid:455)p(cid:396)otei(cid:374) a(cid:374)d l* depe(cid:374)ds o(cid:374) ires i(cid:374) (cid:1009)" (cid:374)o(cid:374) (cid:272)odi(cid:374)g (cid:396)egio(cid:374) Infections in cns, causes inflammatory response with demyelination reminiscent of ms. Tmev infected mice have mononuclear inflammatory response via virus specific cd4+ t cells targeting viru (chronically persists in cns)
