Download Human immunodeficiency virus (HIV)

Ad5 expressing
Gag, Pol and Nef
Immune responses in
control of HIV replication
non-human primates // SIV
extrapolated to
humans // HIV
HIV-1 // SIVcpz
HIV-2 // SIVsm
 in TRIM5α
Prospects for successful HIV vaccine
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:
[email protected] (7MB, mpeg)
Human immunodeficiency virus (HIV)
Retrovirus - Lentivirus
+ssRNA
RT
dsDNA
integrase
=
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
TRANSCRIPTION
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
Genomic organisation of HIV
p7
Structural
p17
p24
proteins for
new particles
gp160
gp120
Regulatory
genes
!
gp41
Sequence variability of HIV proteins
(POSSIBLE EPITOPS)
Fellay J et al. 2007 Science
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)
Polymorphism of HLAs
HLA-B
817
HLA-A
486
The most polymorphic locus
HLA-C
263
on chr 6 and in the human genome
prevalence [%]
20
B8 HLA-B allel
in 8 selected populations
(Bar) – Barbados (MIDDLE AMERICA)
(Van) – Vancouver (NORTH AMERICA)
(Bra) – Brazil (SOUTH AMERICA)
(Côt) – Côte d’Ivore (MIDDLE AFRICA)
(Rus) – Northwest Russia (MIDDLE ASIA)
10
(Jap) – Japan (EAST ASIA)
(Tha) – Thailand (SOUTH ASIA)
(Kwa) – KwaZulu-Natal (SOUTH AFRICA)
0
Bar Van Bra Côt Rus Jap ThaKwa
"These differences are a matter of life and death"
HLA-B*27/57
HLA control of infection
by presenting multiple GAG epitopes
Diversity of AA in position 2 of HIV epitopes that bind HLAs
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
"Keep going!" 
"Keeps going…" 