Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates //...

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

of 14

  • date post

    03-Jan-2016
  • Category

    Documents

  • view

    214
  • download

    1

Embed Size (px)

Transcript of Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates //...

  • Ad5 expressingGag, Pol and Nef

  • HIV-1 // SIVcpzHIV-2 // SIVsm in TRIM5

  • Retrovirus - Lentivirus+ssRNARTdsDNAintegraseTRANSCRIPTIONHuman 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)

  • Retrovirus - Lentivirus+ssRNARTdsDNAintegraseTRANSCRIPTIONHuman immunodeficiency virus (HIV)Primarily: CD4+ TH cells; M; DCLOW1. direct viral killing of infected cells2. increased rates in apoptosis3. HIV specific CD8+ cytotoxic T lymphocyte (CTL) response=

  • IncubationperiodLatencystageAIDS- SIV macaque model: CD8 monoclonal Ab abrogated the declineViral setpointHIV specific CD8+ cytotoxic T lymphocyte (CTL) responseAcuteinfection

  • Genomic organisation of HIV!Structuralproteins fornew particlesRegulatorygenesp7p17p24gp160gp120gp41

  • Sequence variability of HIV proteins(POSSIBLE EPITOPS)

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

  • HLA-B817Polymorphism of HLAsHLA-A486HLA-C263The most polymorphic locuson chr 6 and in the human genome(Bar) Barbados (MIDDLE AMERICA)(Van) Vancouver (NORTH AMERICA)(Bra) Brazil (SOUTH AMERICA)(Ct) Cte dIvore (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 allelin 8 selected populationsHLA-B*27/57

  • HLA control of infectionby presenting multiple GAG epitopes

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

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

  • "Keep going!" "Keeps going"