IISER Bhopal scientists develop novel molecule that can hinder viral transcription of HIV-1 virus

The development could potentially lead to novel drugs and therapies to fight HIV-1

By Seema Prasad
Published: Monday 25 September 2023
3D illustration of HIV Virus. Photo: iStock

Researchers at the Indian Institute of Science Education and Research (IISER) in Bhopal have identified a Circular RNA, ciTRAN, whose role in HIV-1 virus replication has remained unclear for a long time, and also developed a molecule that could hinder viral transcription.

Circular RNA plays a pivotal role in regulating gene expression and is essential for various biological processes. The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown, the researchers explained.

Establishing how ciTRAN modulates the virus’s transcription process, could potentially lead to novel drugs and therapies to fight HIV-1, according to the study published in the peer-reviewed journal Science Advances.

"Using a customized protocol involving direct RNA nanopore sequencing (called circDR-Seq), here, we captured circRNAs from HIV-1–infected T cells (white blood cells) and identified ciTRAN, a circRNA that modulates HIV-1 transcription,” the paper explained.

HIV-1 viral protein R (VpR) is a multifunctional protein that plays specific roles at multiple stages of the HIV-1 viral life cycle and affects anti-HIV functions of the immune cells, another study explained.

“We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with serine/arginine-rich splicing factor 1 (SRSF1), a protein known to repress HIV-1 transcription,” the researchers said in their paper. 

How does this work? The results suggest that HIV-1 hijacks ciTRAN which is generally altered during immunological signaling, inflammation, and viral infection. It further prevents (SRSF1) from doing its job, thereby promoting efficient viral transcription. 

“In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks,” the paper elaborated on the creation of the molecule that interferes with viral transcription.

Lead researcher Dr. Ajit Chande said in a press release, “Characterising 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.”

Chande added, "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.”

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