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

Area of Science:

• Virology
• Molecular Biology
• RNA Biology

Background:

• Circular RNAs (circRNAs) are recognized for their roles in various biological processes.
• The presence and function of viral-encoded circRNAs, particularly in HIV-1, remain largely unexplored.
• Understanding viral RNA elements is crucial for deciphering viral replication and pathogenesis.

Purpose of the Study:

• To investigate the existence and function of HIV-1-encoded circular RNAs.
• To determine the role of any identified viral circRNAs in HIV-1 transcription and pathogenesis.
• To explore the interaction between viral circRNAs and host/viral proteins.

Main Methods:

• Detection of circRNAs using RT-qPCR and northern blot in patient plasma and infected cells.
• Identification of circRNA packaging into HIV-1 virions.
• RNA immunoprecipitation and in vitro pulldown assays to study protein-RNA interactions.

Main Results:

• Successfully detected a novel HIV-1-encoded circRNA (circHIV) in plasma and infected cells.
• Confirmed that circHIV is packaged within HIV-1 virions.
• Demonstrated that circHIV binds to the HIV-1 Tat protein, enhancing viral transcription.

Conclusions:

• HIV-1 encodes a functional circRNA, circHIV, which is a component of infectious virions.
• circHIV acts as a transcriptional regulator by interacting with the Tat protein, thereby promoting HIV-1 pathogenesis.
• This discovery highlights circRNAs as a novel class of viral regulatory elements in HIV-1 infection.