In Vitro HIV-1 LTR Integration into T-Cell Activation Gene CD27 Segment and the Decoy Effect of Modified-Sequence DNA

Abstract

Integration into the host genome is an essential step in the HIV-1 life cycle. However, the host genome sequence that is favored by HIV-1 during integration has never been documented. Here, we report that CD27, a T cell activation gene, includes a sequence that is a target for in vitro HIV-1 cDNA integration. This sequence has a high affinity for integrase, and the target nucleotides responsible for this higher affinity were identified using a crystal microbalance assay. In experiments involving a segment of the CD27 gene, integration converged in the target nucleotides and flanking sequence DNA, indicating that integration is probably dependent upon the secondary structure of the substrate DNA. Notably, decoy modified CD27 sequence DNAs in which the target nucleotides were replaced suppressed integration when accompanying the original CD27 sequence DNA. Our identified CD27 sequence DNA is useful for investigating the biochemistry of integrase and for in vitro assessment of integrase-binding inhibitors.

TNF and TNF Receptor Superfamily Members in HIV infection: New Cellular Targets for Therapy?

“…Ligand for CD27 is CD27L (CD70), a member of TNF ligand superfamily. CD27 plays an important role in the activation of T cells and infection of T cells by HIV-1 [ 67 , 68 ]. One critical feature of HIV-1 life cycle is its integration into the host genome using virus-encoded integrase.…”

“…One critical feature of HIV-1 life cycle is its integration into the host genome using virus-encoded integrase. There are reports describing preference of HIV integration into transcriptionally active genes [ 68 , 69 ]. A recent study shows that HIV-1 integrates into the coding region of CD27 gene in CD4+ T cells which may disturb CD27 open reading frame and hence can hamper the help response of CD4+ T cells [ 68 ].…”

“…There are reports describing preference of HIV integration into transcriptionally active genes [ 68 , 69 ]. A recent study shows that HIV-1 integrates into the coding region of CD27 gene in CD4+ T cells which may disturb CD27 open reading frame and hence can hamper the help response of CD4+ T cells [ 68 ]. This can result in inefficient removal of HIV-1 from CD4+ T cells by cytotoxic CD8+ T cells [ 68 ].…”