Ad5 expressing Gag, Pol and Nef Immune responses in control of HIV replication non-human primates //...
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:firstname.lastname@example.org (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"