Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 45
Dual activity of phosphorothioate CpG-oligodeoxynucleotides on HIV: Reactivation of
latent provirus and inhibition of productive infection in human T cells
Carsten Scheller*1, Stefan Lamla1, Ulf Dittmer2, Axel Rethwilm1, Eleni Koutsilieri1
Institute of Virology and Immunobiology, University of Wuerzburg, Versbacher Strasse
7, 97078 Wuerzburg, Germany
Institute of Virology, UK Essen, Hufelandstrasse 55, 45122 Essen, Germany
* correspondence to: Carsten Scheller, email: scheller@vim.uni-wuerzburg.de
CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor 9 (TLR-9) and trigger
cellular activation in immune cells with antigen-presenting activity, including B-cells and
dendritic cells. Here we show that treatment of the latently HIV-infected T cell line ACH-2
with the CpG ODNs 2006 or 2040 trigger activation of viral gene expression, demonstrating
that CpG-signaling activity can also be found in T cells. In contrast to the stimulating effects
on viral gene transcription in latently-infected cells, CpG ODNs potently suppressed HIV
replication in productively-infected T cells. Inhibition of virus replication was not related to
CpG motifs but was likely caused by the phosphorothioate backbone of the CpG ODNs,
probably by interfering with the viral enzyme reverse transcriptase. These results point to a
novel role of CpG-sequences in the development of immune activation therapies to
accomplish eradication of HIV from its latent T cell reservoir in vivo.
- 172 -