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

Subject :Science and tech

Section: Biotechnology

Context:

Researchers at the Indian Institute of Science Education and Research (IISER) in Bhopal have identified a Circular RNA virus, 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 virus- ciTRAN:

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.
Establishing how ciTRAN modulates the virus’s transcription process, could potentially lead to novel drugs and therapies to fight HIV-1.
Using a customized protocol involving direct RNA nanopore sequencing (called circDR-Seq), the researchers capturedcircRNAs from HIV-1–infected T cells (white blood cells) and identified ciTRAN, a circRNA that modulates HIV-1 transcription.
Characterizing circular RNA can be tricky because it usually is less abundant, making it further challenging to detect in the native form.

HIV-1:

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.
The researchers found that the 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.

How does this work?

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.
The researchers also demonstrated 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.

Significance of the findings:

The 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.

Source: DTE