Circular RNA: Unveiling HIV-1 Multiplication Mechanism

Scientists Identify Circular RNA that Plays Key Role in HIV Replication

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Scientists from the Indian Institute of Science Education and Research (IISER), Bhopal, have made significant progress in finding a cure for the human immunodeficiency virus (HIV). In a groundbreaking discovery, they have identified a circular RNA called ciTRAN that plays a crucial role in the replication of the HIV-1 virus, which causes AIDS. This discovery opens up new avenues for the development of novel therapeutic interventions for the disease, which has already claimed 40.4 million lives globally.

For a long time, the involvement of circular RNA (circRNA) in HIV-1 replication has remained unclear. But now, the researchers at IISER Bhopal, led by Dr. Ajit Chande from the Department of Biological Sciences, have shed light on how ciTRAN enhances the efficiency of HIV replication by facilitating the copying of genetic information from the virus.

Ribonucleic acid (RNA) is a fundamental molecule responsible for carrying genetic information in living cells and aiding in protein production. Most RNAs have a linear structure with free ends, but circRNA forms a closed-loop structure. These circRNAs play a crucial role in regulating gene expression and various biological processes. However, their involvement in HIV-1 replication has been elusive until now.

Dr. Chande explained that characterizing circRNA is complex because it is often less abundant, making its detection in its native form challenging. It’s comparable to following a complicated recipe. Additionally, during viral infections, the vast amount of viral information can overshadow less common RNA molecules like circRNA. Therefore, innovative approaches were needed to identify and understand the roles of these less common RNA molecules.

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To overcome these challenges, the researchers developed a pioneering approach called ‘circDR-Seq.’ This method allowed them to successfully capture circRNAs from T-cells (white blood cells) infected with the HIV-1 virus. Using this technique, they pinpointed the specific circRNA ciTRAN, which plays a critical role in the virus’s multiplication.

Dr. Chande revealed that the HIV-1 virus hijacks host-encoded ciTRAN to multiply efficiently. This discovery unveils a previously unknown facet of how viruses, including HIV-1, overcome transmission barriers. Apart from this groundbreaking discovery, the researchers also developed a small protein molecule capable of inhibiting viral transcription, particularly concerning virally-induced ciTRAN. By demonstrating how ciTRAN fuels the virus’s replication, this study opens up promising paths for the development of novel therapeutic interventions.

Professor Gobardhan Das, Director of IISER Bhopal, expressed his excitement about the research, stating that it opens up new lines of investigation and may provide new leads for host-directed treatments.

The identification of ciTRAN’s role in HIV-1 multiplication represents a major breakthrough in HIV research. This newfound understanding of viral mechanisms and the development of a molecule capable of inhibiting viral transcription bring us one step closer to effective treatments not only for HIV-1 but also for other viral infections. According to a report by the World Health Organization (WHO), in 2022 alone, 630,000 people died from HIV-related causes, and 1.3 million people acquired HIV. Currently, there is no cure for HIV infection. But with ongoing research and these groundbreaking discoveries, there is hope for a future where effective treatments can combat this devastating virus.

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