Grace Chen

Circular RNAs (circRNAs) are a unique class of RNA transcripts distinguished by their closed loop structure that lacks 5’ and 3’ RNA ends. Initially overlooked as accidental byproducts of transcription, circRNAs have recently garnered significant attention for their newfound roles in many biological processes underpinning cellular homeostasis and disease pathogenesis. We have performed a genome-wide analysis to survey the expression of non-polyadenylated, circular transcripts in T-cells infected with Human Immunodeficiency Virus type 1 (HIV-1). We discover a novel viral circRNA encoded by a central region of the HIV-1 genome, marking the first demonstration of circRNA expression from an RNA retrovirus. We also detect this viral circRNA in patient-derived plasma, highlighting its physiological relevance and potential contribution to pathogenesis in vivo. Mechanistic investigations revealed that virions encapsulate this viral circRNA and, upon expression in cells, circHIV interacts with the HIV-1 trans-activator of transcription (Tat) protein to enhance transcription from the integrated proviral genome. Notably, reducing circHIV levels in vitro led to a decrease in viral replication, underscoring its potential as a therapeutic target. Taken together, our findings shed light on a previously unrecognized aspect of HIV-1 gene expression, revealing the ability of HIV-1 to generate circularized, noncoding RNA with a special role in regulating its own genomic transcription.