HIV Replication and Latency: The Role of RNA and DNA G-quadruplexes.
G-quadruplexes are guanine rich nucleic acid structures capable of forming a four-stranded structure. DNA G-quadruplexes have been identified in telomeric DNA as well as more recently in mammalian chromosomal DNA - and are considered attractive targets in anti-cancer drug development studies.
We have recently shown that guanine-rich sequences in the HIV-1 genome can adopt G-quadruplex structures in both viral RNA and DNA. Viral RNA G-quadruplexes support genome dimerization and may facilitate viral recombination, which contributes to viral diversity.
We have also identified G-quadruplexes in the promoter region of HIV-1 proviral DNA (Sp1 binding sites). This suggests that these structures may also contribute to the regulation of viral gene expression (i.e., regulation of latency and reactivation). Our current research focuses on understanding the role of G-quadruplexes in HIV-1 DNA, and determining whether these structures may represent a new target for antiviral therapies.