Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome

• Main Authors: De Nicola, Beatrice, Lech, Christopher J., Heddi, Brahim, Regmi, Sagar, Frasson, Ilaria, Perrone, Rosalba, Richter, Sara N., Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2018
• Subjects: Nuclear Magnetic Resonance (NMR); DRNTU::Science::Physics; Long Terminal Repeat (LTR)
• Online Access: https://hdl.handle.net/10356/88976; http://hdl.handle.net/10220/46042
• Institution: Nanyang Technological University

The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.