Commentary: Can AFM Reveal Global Viral RNA Structure?

A variety of structural motifs in single-stranded viral genomes have been shown to play important roles in guiding key steps in the lifecycle of many viruses [1]. However, most viral genomes are in excess of 1 kb in length, and available technologies generally lack the ability to study the global structural arrangement of long RNA molecules in a single experiment, causing the structures of many RNA molecules to be gradually pieced together over time. To address these issues, we have developed a new high-throughput method using Atomic Force Microscopy (AFM) imaging combined with automated analytic tools to extract information about the global secondary and tertiary structure of long single-stranded nucleic acids (u003e1 kb), mainly focusing on the 9.7 kb Hepatitis C virus (HCV) genome [2,3]. In recent years, the importance of gaining a detailed understanding of the viral lifecycle and the molecular structures guiding viral processes is reflected in the development of targeted antivirals against the NS3 protease, the NS5B polymerase, the NS5A proteins, cyclophilin A, and miRNA-122 [4]. Our method shows great promise for being able to further refine the molecular details of viral processes throughout the lifecycle of the virus, which can be instrumental in the refinement of antiviral strategies.