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Dual Activity of Phosphorothioate CpG Oligodeoxynucleotides on HIV
Author(s) -
SCHELLER CARSTEN,
ULLRICH ANETT,
LAMLA STEFAN,
DITTMER ULF,
RETHWILM AXEL,
KOUTSILIERI ELENI
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.095
Subject(s) - cpg oligodeoxynucleotide , cpg site , biology , tlr9 , virus , toll like receptor 9 , virology , viral replication , immune system , gene , microbiology and biotechnology , gene expression , immunology , dna methylation , genetics
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.