G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide

Enrico Lavezzo; Michele Berselli; Ilaria Frasson; Rosalba Perrone; Giorgio Palù; Alessandra R. Brazzale; Sara N. Richter; Stefano Toppo

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/344127 doi: bioRxiv preprint were stabilized by G4 ligands with consequent inhibition of viral DNA replication (Artusi et al. 2015; Callegaro et al. 2017) . A G4 ligand and its interaction with the telomeric repeats present in the HHV-6 genome were responsible for inhibition of human herpes virus-6 (HHV-6) genome integration into the host cell chromosome (Gilbert-Girard et al. 2017) . Similarly, G4 stabilizing compounds led to a reduction in Kaposi's sarcoma associated herpesvirus (KSHV) DNA replication and disrupted maintenance of the virus latent state (Madireddy et al. 2016 ). In the Epstein-Barr virus (EBV), RNA G4s were implicated in the regulation of viral DNA replication and translation (Norseen et al. 2009; Murat et al. 2014 ) and in the delay of viral antigen-specific T cells priming ). In addition, the interaction of nucleolin with EBNA1 mRNA G4 mediated the virus immune evasion (Lista et al. 2017) . In human papillomavirus (HPV), the presence of DNA G4s at the genome level was reported (Tluckova et al. 2013) . In ssDNA viruses, the presence of G4s in the adeno-associated virus genome and their interaction with nucleophosmin were shown to repress virus entry and replication (Satkunanathan et al. 2017) . In ssRNA (+) viruses, RNA G4s were described in the genomes of flaviviruses (e.g. Zika) and hepatitis C virus (HCV) (Fleming et al. 2016; Wang et al. 2016a ). In the severe acute respiratory syndrome (SARS) coronavirus, a viral protein domain necessary for viral genome replication/transcription specifically binds RNA G4s (Tan et al. 2009; Kusov et al. 2015) . RNA G4s were also found in the ssRNA (-) Ebola virus genome (Wang et al. 2016b) . In hepatis B virus (HBV), the only member of dsDNA viruses with RT activity, stabilization of a G4 in the promoter of the envelope gene increased transcription and virion secretion (Biswas et al. 2017) . Functionally significant G4s were identified in the human immunodeficiency virus (HIV), a retrovirus belonging to group 6 (Table 1). G4s were described both in the RNA and DNA proviral genome (Perrone et al. 2013a; Perrone et al. 2014; Piekna-Przybylska et al. 2014) : in the latter, clusters of G4s were reported in the unique long terminal repeat (LTR) promoter (Perrone et al. 2013a; Amrane et al. 2014 ) and in the Nef coding region (Perrone et al. 2013b ). The cellular proteins nucleolin and hnRNP A2/B1 regulate the G4/ds equilibrium in the LTR promoter (Tosoni et al. 2015; Lago et al. 2017; Scalabrin et al. 2017 ) and G4 ligands induced author/funder. All rights reserved. No reuse allowed without permission.