2009_IFN_System

2009_IFN_System - @ (D Virus Infection C) Virus...

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Unformatted text preview: @ (D Virus Infection C) Virus Multiplication )5 TABLE 3. ClasSItication and mayor teamres of the interferons Type l lFN Type H “m f (lFN-u/B) (tFN—y) lFN-u (at least —- 14 potentially functional genes in humans) lFN~B IFN-in iFN-r Chromosome 9 Chromosome 12 (human) (human) Chromosome 4 Chromosome to (mouse) (mouse) No inlrons Three introns Proteins' Receptors l Sublamilies Structural genes 5 i t i I IFN-u 155-165 amino acids (a.a.) lFN-B: 166 a.a‘ IFN-w: 172 a.& IFN-r: 172 a.a. Genes tor two chains located on chromo- some 21 (human) and chromosome 16 (mouse) 146 are. (forms dimer) Gene lor u chain on chromosome 6 (human) and chromosome l0 (mouse) Gene for 3 chain on chromosome r 21 (human) and chromosome 16 (mouse) Interferon System Inhibition of Virus Multiplication Infected (Stimulated) Cell IFN Production NUCLEUS Infectious Progeny Virus 0 o STAT YST AT 1 Interferon-Treated Cell IFN Action IRP IFN—Regulated Proteins CE. Samuel MCDB 134 IFN-Regulated Proteins PKR (ds RNA) Ch 2 ADAR (ds RNA) Ch 1 2, 5-OAS (ds RNA) Ch 12 RNase L (2,5A) Ch 1 Mx (GTP) Ch 21 INTERFEHON SIGNAL TRANSDUCTION PA TH WA Y CYTOPLASM 030 r—> MHCIl W F S,X,X2,Y —J lFN-a/B \I\!\I\I\I\I\ L—isnE-J MHCl PKR ADAR 2'5‘OAS Mx Olher / TABLE 6. Multiple steps of viral replication inhibited by interferons Affected step Viruses Responsible IFN-induced proteins ' ‘ ' SV40. retroviruses ' Unknown figgécfirigéam' uncoatmg Influenza, VSV. HSV Mx proteins (and others?) Translation Picornaviruses 2-S(A) synthetase/HNAse L Reoviruses. adenovirus, vaccinia, DsRNA-dependent protein kinase (PKR) VSV, influenza Late: Maturation, assembly, release Retrovirus, VSV, HSV Unknown Antiviral Actions of Interferon Single-Cell Responses Hepatitis C Amgen [nfergen lFN»acon : IFN IFN IFN IFN i _ l ', Oligoadenylate Adenosine Other Proteins l Prom“ Kmase Synthetase Deaminase j Inactive Inacm’e (Multiple Forms: nuclear M" Proteins g m dSRNA m and cytoplasmic) i 1 4m 55 RNA i A Nitric Oxide 5 _ ' Oligoadenylate dSHNA dsRNA Synthase ‘ Protein Kmase Sythetase A:U I:C Active Active ‘ U ‘ Ribosome-associated Multiple Forms: nuclear , , x: , i ( > ( and cytoplasmic) RNA Edmng 3 U :3 a i finitiation A Phosphorylated ATP A 2', 5'.o|igo g IE , Factor Initiation Factor . - .9 a ’5 .1 a) :u ; AMP Adenylic ACId ‘ = a. 9.: a. V ielF-Zcx elF-2a ® U (2 5A)»: ‘ 2 .2.) E Pt Phosphodiesterase ‘ ‘i E “ ‘“ ‘ ' Phos hatase o 5 issues) v 50% h 5 v ’ 5 e E .34 E a. E, m o . i —> '5 cu u _} = a mRNA Translation EndORNase EndORNase s: .c a v ? inhibition Inactive Active 3 E 5 3 : l 5'; E g a . ' 55 : U ,7: i I RNA Degradation ‘ g E w L“ 5* g E < r: 'o 3 ‘E’ '-= < E E H v E I: 42 e ‘5 E % E i , r‘ a: E 3 l ‘” “9 : Z 6 3 83618153 m [a] ' ‘ * E i a t .. ,1" LPS .F iii Umnamweni‘e ‘CPG ' E 1 ttpopmtelns V B93 n ' bacteria DNA ‘ " Z 2‘; , V , i m LL. V... t i .1 “ SS :9: ‘E 2 t m ? i5 t? ‘3 ‘ :5 z z z 3 i e e e My088 MyD88 induction of type I lFNs (TLR 3,4,7,8,9) and Inflammatory Cytokines (all TLRs) via adaptor molecules and activated transcription factors Hepatitis C PEG—Intron Schering Peg-IFN—aZb ...
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This note was uploaded on 06/08/2010 for the course MCDB 134 taught by Professor Samuels during the Spring '10 term at UCSB.

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2009_IFN_System - @ (D Virus Infection C) Virus...

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