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Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates // SIV extrapolated to humans // HIV Prospects for.

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Presentation on theme: "Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates // SIV extrapolated to humans // HIV Prospects for."— Presentation transcript:

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2 Ad5 expressing Gag, Pol and Nef

3 Immune responses in control of HIV replication non-human primates // SIV extrapolated to humans // HIV Prospects for successful HIV vaccine HIV-1 // SIV cpz HIV-2 // SIV sm  in TRIM5α

4 Retrovirus - Lentivirus +ssRNARTdsDNAintegrase TRANSCRIPTION Human immunodeficiency virus (HIV) = * * You can the movie from here in the Janeway 7th Edition attached CD. But you also can ask me if you do not have the book: dolowschiak.tamas@mh-hannover.de (7MB, mpeg)

5 Retrovirus - Lentivirus +ssRNARTdsDNAintegrase TRANSCRIPTION Human immunodeficiency virus (HIV) Primarily: CD4 + T H cells; MØ; DC LOW 1. direct viral killing of infected cells 2. increased rates in apoptosis 3. HIV specific CD8+ cytotoxic T lymphocyte (CTL) response =

6 Incubation period Latency stage AIDS - SIV macaque model: CD8 monoclonal Ab abrogated the decline Viral setpoint HIV specific CD8 + cytotoxic T lymphocyte (CTL) response Acute infection

7 Genomic organisation of HIV ! Structural proteins for new particles Regulatory genes p7p17p24 gp160 gp120gp41

8 Sequence variability of HIV proteins (POSSIBLE EPITOPS)

9 Fellay J et al. 2007 Science The six most highly significant determinants within the MHC region (short arm of chr 6) HLAs: encode of α-chains (ß 2 -microglobulin: chr 15) TO STUDY HUMAN GENETIC VARIABILITY

10 HLA-B 817 Polymorphism of HLAs HLA-A 486 HLA-C 263 The most polymorphic locus on chr 6 and in the human genome (Bar) – Barbados ( MIDDLE AMERICA ) (Van) – Vancouver ( NORTH AMERICA ) (Bra) – Brazil ( SOUTH AMERICA ) (Côt) – Côte d’Ivore ( MIDDLE AFRICA ) (Rus) – Northwest Russia ( MIDDLE ASIA ) (Jap) – Japan ( EAST ASIA ) (Tha) – Thailand ( SOUTH ASIA ) (Kwa) – KwaZulu-Natal ( SOUTH AFRICA ) "These differences are a matter of life and death" B8 HLA-B allel in 8 selected populations HLA-B*27/57

11 HLA control of infection by presenting multiple GAG epitopes

12 Diversity of AA in position 2 of HIV epitopes that bind HLAs

13 Summary "take home message" Single AA differences may have crucial consequences in terms of outcome from particular infections MHC class I molecules associated with control of HIV replication in humans + SIV replication in macaque models can have similar or dissimilar peptide-binding motifs HLA-B*27/57: strong association – present several Gag epitopes targeting of Gag epitopes by CD8 + T cells can result immune control of viral replication

14 "Keep going!" "Keeps going…" 


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