HIV-1-encoded circular RNA enhances viral transcription through Tat binding.

Circular RNAs (circRNAs) are single-stranded RNAs that form a covalently closed loop without 5' and 3' ends. From their own genomes, RNA viruses can encode circRNAs that play important roles during infection, but whether this is the case for HIV remains unclear. Here we detect an HIV-1-encoded viral circRNA (termed circHIV) in plasma from 18 people living with HIV and in infected primary cells and T-cell lines using RT-qPCR and northern blot. We find that this viral circRNA is packaged within HIV-1 virions and binds to the HIV-1 Tat protein upon expression in cells, which enhances transcription from the viral promoter, as shown by RNA immunoprecipitation and in vitro pulldown assays. Our study sheds light on a previously overlooked component of HIV-1 transcription, revealing the ability of circRNAs to act as transcriptional regulators that drive viral pathogenesis.