Contrasting roles for G-quadruplexes in regulating human Bcl-2 and virus homologues KSHV KS-Bcl-2 and EBV BHRF1

Journal article

AbstractHerpesviruses are known to acquire several genes from their hosts during evolution. We found that a significant proportion of virus homologues encoded by HSV-1, HSV-2, EBV and KSHV and their human counterparts contain G-quadruplex motifs in their promoters. We sought to understand the role of G-quadruplexes in the regulatory regions of viral Bcl-2 homologues encoded by KSHV (KS-Bcl-2) and EBV (BHRF1). We demonstrate that the KSHV KS-Bcl-2 and the EBV BHRF1 promoter G-quadruplex motifs (KSHV-GQ and EBV-GQ) form stable intramolecular G-quadruplexes. Ligand-mediated stabilization of KS-Bcl-2 and BHRF1 promoter G-quadruplexes significantly increased the promoter activity resulting in enhanced transcription of these viral Bcl-2 homologues. Mutations disrupting KSHV-GQ and EBV-GQ inhibit promoter activity and render the KS-Bcl-2 and the BHRF1 promoters non-responsive to G-quadruplex ligand. In contrast, promoter G-quadruplexes of human bcl-2 gene inhibit promoter activity. Further, KS-Bcl-2 and BHRF1 promoter G-quadruplexes augment RTA (a virus-encoded transcription factor)-mediated increase in viral bcl-2 promoter activity. In sum, this work highlights how human herpesviruses have evolved to exploit promoter G-quadruplexes to regulate virus homologues to counter their cellular counterparts.

Authors: Kumar, S; Ramamurthy, C; Choudhary, D; Sekar, A; Patra, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Scientific Reports
• Volume: 12
• Issue: 1
• Pages: 5019-5019
• Article number: 5019
• Publication date: 2022-03-23
• DOI: 10.1038/s41598-022-08161-9
• EISSN: 2045-2322
• ISSN: 2045-2322
• Language: English
• Keywords: Virology; Molecular biology; Biology; G-quadruplex; Transcription (linguistics); Promoter; Genetics; DNA; Gene expression; Transcription factor; Virus; Gene