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Ad5 expressing Gag , Pol and Nef

Ad5 expressing Gag , Pol and Nef. non-human primates // SIV extrapolated to humans // HIV. Immune responses in control of HIV replication. Prospects for successful HIV vaccine. HIV-1 // SIV cpz. HIV-2 // SIV sm.  in TRIM5 α. Human immunodeficiency virus (HIV).

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Ad5 expressing Gag , Pol and Nef

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  1. Ad5 expressing Gag, Pol and Nef

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

  3. Human immunodeficiency virus (HIV) Retrovirus - Lentivirus +ssRNA RT dsDNA integrase = TRANSCRIPTION * * 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)

  4. Human immunodeficiency virus (HIV) Retrovirus - Lentivirus +ssRNA RT dsDNA integrase = TRANSCRIPTION Primarily: CD4+ TH 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

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

  6. Genomic organisation of HIV p7 p17 p24 Structural proteins for new particles gp160 gp120 gp41 Regulatory genes !

  7. Sequence variability of HIV proteins (POSSIBLE EPITOPS)

  8. Fellay J et al. 2007Science The six most highly significant determinants within the MHC region TO STUDY HUMAN GENETIC VARIABILITY (short arm of chr 6) HLAs: encode of α-chains (ß2-microglobulin: chr 15)

  9. Polymorphism of HLAs HLA-B 817 HLA-A 486 HLA-C 263 The most polymorphic locus on chr 6 and in the human genome (Bar) – Barbados (MIDDLE AMERICA) B8 HLA-B allel in 8 selected populations (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" HLA-B*27/57

  10. HLA control of infection by presenting multiple GAG epitopes

  11. Diversity of AA in position 2 of HIV epitopes that bind HLAs

  12. Summary • 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 "take home message" Single AA differences may have crucial consequences in terms of outcome from particular infections

  13. "Keep going!" "Keeps going…"

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