7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


TUAA01 Viral and Immune-Targeted Interventions: Hit Me with Your Best Shot
  Oral Abstract Session : Track A Basic Sciences
Venue: Session Room 2
Time: 02.07.2013, 16:30 - 18:00
Co-Chairs: Guido Silvestri, United States
Sharon Lewin, Australia

16:30
TUAA0101
Abstract
Destruction of the residual active HIV-1 reservoir by Env-specific immunotoxin
P.W. Denton1, J. Long1, N. Archin1, S. Wietgrefe2, S. Choudahry1, C. Sykes3, K. Yang3, M.G. Hudgens4, I. Pastan5, E.A. Berger6, A. Haase2, A. Kashuba3, D.M. Margolis1, J.V. Garcia1
1University of North Carolina at Chapel Hill, Internal Medicine/Infectious Diseases, Chapel Hill, United States, 2University of Minnesota, Minneapolis, United States, 3University of North Carolina at Chapel Hill, School of Pharmacy, Chapel Hill, United States, 4University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Chapel Hill, United States, 5National Cancer Institute/NIH, Bethesda, United States, 6National Institute of Allergy and Infectious Diseases/NIH, Bethesda, United States

16:45
TUAA0102
Abstract
Targeting HIV-1 persistence in CD4 T memory stem cells by pharmaceutical inhibition of beta-catenin
M. Buzon1, H. Sun1,2, C. Li1, E. Martin-Gayo1, A. Shaw1, E. Rosenberg3, F. Pereyra1, B. Walker1, X. Yu1, M. Lichterfeld3
1Ragon Institute of MGH, MIT and Harvard, Cambridge, United States, 2AIDS Research Center, China Medical University, Shenyang, China, 3Massachusetts General Hospital, Department of Medicine, Boston, United States

17:15
TUAA0104
Abstract
Powerpoint
DC infected by the ANRS MVAHIV vaccine candidate primes NK cells with anti-HIV specific activity through a mechanism involving NKG2D and NKp46 on NK cells and membrane-bound IL-15 on DC
U.Y. Moreno Nieves1, J.-S. Cummings1, V. Arnold1, A. Gilbert1, K. Yarbrough1, C. Didier1, Y. Lévy2, F. Barré-Sinoussi1, D. Scott-Algara1, ANRS HIV Vaccine Network (AHVN)
1Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France, 2INSERM U955, Groupe Henri-Mondor Albert-Chenevier, Créteil, France

17:30
TUAA0106
Abstract
Powerpoint
Webcast
The HIV-1 splicing inhibitor, SPL-464, compromises viral replication in vitro and induces a long lasting anti-viral effect in humanized mice infected with HIV-1
N. Campos1, R. Myburgh2, A. Garcel1, A. Vautrin3, D. Scherrer1, M.A. Wainberg4, R. Speck2, J. Tazi3
1Splicos, Montpellier, France, 2University Hospital of Zürich, Zürich, Switzerland, 3University of Montpellier-IUF, IGMM-CNRS UMR 5535, Montpellier, France, 4McGill University, Montreal, Canada

17:30
TUAA0107
Webcast
Moderated discussion

Powerpoints presentations
DC infected by the ANRS MVAHIV vaccine candidate primes NK cells with anti-HIV specific activity through a mechanism involving NKG2D and NKp46 on NK cells and membrane-bound IL-15 on DC - Uriel Yojanan Moreno Nieves

The HIV-1 splicing inhibitor, SPL-464, compromises viral replication in vitro and induces a long lasting anti-viral effect in humanized mice infected with HIV-1 - Jamal Tazi



Rapporteur report

Track A report by Nichole Klatt


Viral and Immune-Targeted Interventions: Hit Me with Your Best Shot

 

Victor Garcia: Destruction of the residual active HIV-1 reservoir by Env-specific immunotoxin

 

Experimental Goal: To eliminate cellular reservoirs of HIV that continue to actively produce virus in tissue compartments despite suppression of plasma viremia with ARVs

         -Assessed tissue penetration of ARVs in vivo in BLT mice

         -3B3-PE38 immunotoxin (antibody directed to env and carrying pseudomonas toxin) to reduce HIV RNA

 

Results:

-ARVs + 3B3-PE38 reduced HIV RNA as much as 1,000 fold in tissues and overall 0.8 logs

         -mechanism is loss of productively infected cells

 

 

Mathias Lichterfield: Targeting HIV-1 persistence in CD4 T memory stem cells by pharmaceutical inhibition of beta-catenin

 

-HIV is persistent in CD4+ T stem cell memory cells (Tscm) and central memory (Tcm) cells

-Hierarchy of genetic distance in different CD4+ T cells that demonstrates Tscm may be longest lived and most durable reservoir

-HDACi turns HIV genes on

-Beta catenin inhibitors induce differentiation of Tscm and Tcm

         -synergize HDACi and Beta-catenin inhibitors to eradicate HIV?

 

Uriel Moreno-Nieves: DC infected by the ANRS MVAHIV vaccine candidate primes NK cells with anti-HIV specific activity through a mechanism involving NKG2D and NKp46 on NK cells and membrane-bound IL-15 on DC

 

-NK cells stimulated by MVAHIV – infected dendritic cells (DC) are able to control virus infection of DCs

         -Can NK cells control infection in other cell types?

-MVA priming increases control of HIV infection by NK cells

         -Modulated by NKG2D

         -Blockade of NKG2D decreases membrane bound IL-15

         -IL-15 is important for MVA priming of NKs

-Suggests NK cells may be important in vaccine efficacy

 

 

Jamal Tazi: The HIV-1 splicing inhibitor, SPL-464, compromises viral replication in vitro and induces a long lasting anti-viral effect in humanized mice infected with HIV-1

 

-Alternate splicing of HIV after cell infection initiates replication

-HIV-1 RNA has weak 3’ splice sites, dependent on regulators that target HIV sequences

-Splicos has a library of small chemical compounds targeting splicing machinery, including SPL-464

-SPL-464 inhibits virus replication in macrophages from human donors

-SPL-464 reduces viral load & rescues CD8/CD4 ratio in humanized mice

 

 

 




   

    The organizers reserve the right to amend the programme.