Circular RNA functions in HIV-1 infection

Circular RNAs (circRNAs) are covalently closed RNA molecules with increasingly recognized roles in post-transcriptional gene regulation, immune signalling, and host–pathogen interactions. Although circRNAs have been characterized across diverse biological contexts, their roles in viral infection, particularly HIV-1, remain an underexplored area of RNA biology. Here, we review current knowledge of circRNA function in HIV-1 infection, organized into three major themes. First, we examine host-derived circRNAs, which are broadly dysregulated during infection and correlate with viral load, immune status, and antiretroviral therapy response. Second, we discuss viral-derived circRNAs, highlighting emerging evidence that HIV-1 encodes functional circRNA isoforms capable of modulating viral replication and transcription. Finally, we review synthetic circRNA-based approaches that exploit key viral RNA–protein interactions as potential antiviral tools. Collectively, these findings underscore the expanding functional roles of circRNAs in HIV-1 infection and highlight their potential as both therapeutic targets and molecular tools for future research.