Dual activity of phosphorothioate CpG oligodeoxynucleotides on HIV: reactivation of latent provirus and inhibition of productive infection in human T cells.
CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor-9 (TLR-9) and activate immune cells with antigen-presenting activity, including B cells and dendritic cells. Here we show that treatment of the latently human immunodeficiency virus (HIV)-infected T cell line ACH-2 with the CpG ODNs 2006 or 2040 triggers activation of viral gene expression, demonstrating that CpG-signaling activity can also be found in T cells. The CpG ODNs g12AAC and g12GTC had no effect on virus reactivation. In contrast to the stimulating effects on viral gene expression in latently infected cells, CpG ODNs potently suppressed HIV replication in productively infected MT4 T cells or PBLs. Inhibition of virus replication was not related to the CpG motif but similarly occurred with non-CpG phosphorothioate (PTO)-ODNs. Thus, virus inhibition was likely caused by the PTO backbone of the CpG ODNs, probably by interfering with events prior to integration of the viral cDNA into the host genome. The ability of CpG PTO-ODNs to trigger reactivation of latent HIV in combination with their antiviral activity on productive infection makes this substance class an interesting candidate for further test to asses their potential as supplements in HIV therapy.
Scheller
Carsten
C
Institute of Virology and Immunobiology, University of Wuerzburg, Versbacher Strasse 7, 97078 Wuerzburg, Germany. scheller@vim.uni-wuerzburg.de
Ullrich
Anett
A
Lamla
Stefan
S
Dittmer
Ulf
U
Rethwilm
Axel
A
Koutsilieri
Eleni
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D018899:CpG Islands / Q000502:physiology*; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011533:Proviruses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014775:Virus Activation / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology
D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides