G-quadruplexes in viruses: function and potential therapeutic applications

Abstract

G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.

Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells

“…Besides eukaryotes, G4 relevance and presence have recently emerged also in prokaryotes (9,10) and viruses (11). The presence of functionally significant G4 DNA motifs in the human immunodeficiency virus (HIV) has been reported by us and others both in the promoter (12–14) and Nef coding regions (15).…”

The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

“…Recently, the presence of G4s in viruses and their involvement in key steps of viral infection has been provided6. G4s have been reported in the SARS coronavirus7, the human papilloma, hepatitis C, Zika and Ebola virus genomes891011.…”

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

“…Many G-rich sequences having the potential to adopt a G4 structure are associated with cellular processes. They can be found in telomeres, oncogene promoters, non-translated RNA regions, and in virus genomes [76,[84][85][86][87][88]. Therefore, they are considered as potential clinical targets for drugs to interfere with processes like telomere maintenance and function, transcription and translation regulation, cellular localization of RNAs, virus inhibition [84,85,[89][90][91][92][93][94].…”