Researchers from Indian Institute of Science Education and Research Bhopal (IISER Bhopal) identified a specific circular RNA (circRNA) called ‘ciTRAN’, which plays a crucial role in multiplication of the AIDS-causing HIV-1 virus within the human body.
Led by Dr. Ajit Chande from Department of Biological Sciences, IISER Bhopal, this research shows how ciTRAN helps the process of copying genetic information from the virus, essentially helping the virus multiply more efficiently.
The details of this study have been published in the reputed peer-reviewed journal Science Advances (https://doi.org/10.1126/sciadv.adh9170) in a paper co-authored by Vipin Bhardwaj, Aman Singh, Aditi Choudhary, Rishikesh Dalavi, Dr. Lalchhanhima Ralte, Dr. Richard Chawngthu, Dr. Nachimuthu Senthilkumar, Dr. Nagarjun Vijay and Dr Ajit Chande.
The RNA or Ribonucleic acid is a molecule in living cells that carries genetic information and helps in the production of proteins. RNAs are in general straight-chain, free-end structures but one form of RNA called ‘circRNA’ forms a closed-loop. The circRNA plays a pivotal role in regulating gene expression and is essential for various biological processes. Its role in HIV-1 replication has remained unclear for a long time.
Explaining the rationale for the study, Dr. Ajit Chande said, “Characterizing circular RNA can be tricky because it usually is less abundant, making it further challenging to detect in the native form. It is like trying to follow a complicated recipe. Additionally, when we look at RNAs during viral infections, there's so much information from the virus that it can make it hard to find the less common ones like circular RNA. So, we needed to devise different ways to spot these less common RNA molecules to understand their roles.”
The researchers developed a novel approach called ‘circDR-Seq’, to successfully capture circRNAs from T-cells (white blood cells) infected with the HIV-1 virus and identified a specific circRNA named ciTRAN, which plays an important role in the multiplication of the virus.
Dr. Ajit Chande, the lead researcher further said, "Our results indicate that HIV-1 virus hijacks this host-encoded ciTRAN in such a way that it can use it to multiply efficiently. This discovery uncovers a previously unknown aspect of how viruses like HIV-1 overcome transmission barriers.”
Prof. Gobardhan Das, Director, IISER Bhopal, expressed his excitement over this pivotal discovery. “This work opens up new lines of investigations and may provide new leads for host-directed treatments,” he added.
Another important result from this research was that the researchers developed a small protein molecule that can inhibit viral transcription, in the context of virally-induced ciTRAN. By showing how ciTRAN promotes the virus's ability to multiply efficiently, this study offers promising avenues for the development of novel therapeutic interventions. Moreover, the creation of a molecule capable of inhibiting viral transcription represents a significant leap in our understanding of combating HIV-1 and potentially other viruses.