Ad5 expressing

Gag, Pol and Nef

Immune responses in

control of HIV replication non-human primates // SIV

extrapolated to

humans // HIV

Prospects for successful HIV vaccine

HIV-1 // SIVcpz

HIV-2 // SIVsm

in TRIM5α

Retrovirus - Lentivirus

+ssRNA RT dsDNA integrase

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)

Retrovirus - Lentivirus

+ssRNA RT dsDNA integrase

TRANSCRIPTION

Human immunodeficiency virus (HIV)

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

=

Incubationperiod

Latencystage

AIDS

- SIV macaque model: CD8 monoclonal Ab abrogated the decline

Viral setpoint

HIV specific CD8+ cytotoxic T lymphocyte (CTL) response

Acuteinfection

Genomic organisation of HIV

!

Structural

proteins for

new particles

Regulatory

genes

p7 p17 p24

gp160

gp120 gp41

Sequence variability of HIV proteins

(POSSIBLE EPITOPS)

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

(ß2-microglobulin: chr 15)

TO STUDY HUMAN GENETIC VARIABILITY

HLA-B817

Polymorphism of HLAs

HLA-A486 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 allelin 8 selected populations

Bar Van Bra Côt Rus Jap ThaKwa0

10

20

pre

vale

nce

[%

]

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

"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

"Keep going!" "Keeps going…"