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Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis

Public Release: 31-Mar-2020

The article by Dr.Patrick E.H. Jackson* et al is published in Current HIV Research, 2020

A team of researchers led by Patrick E. H. Jackson at the Myles H. Thaler Center for HIV and Human Retrovirus Research, University of Virginia, Charlottesville, Virginia, USA, has published a review on the subject of the HIV-1 Rev Regulatory complex (dubbed the HIV-1 Rev Regulatory Axis) in the journal, Current HIV Research. HIV-1 Rev Regulatory Axis is comprised of 2 key components which are necessary to transport viral mRNAs out of the nucleus into the cytoplasm. These components are Rev - a viral protein, and an RNA secondary structure found in called the Rev Response Element (RRE). The RRE is found in all HIV mRNA sequences, and it binds with Rev (to form the Rev-RRE ribonucleoprotein complex), in combination with various cellular factors to overcome cellular defense mechanisms that normally block the exit of foreign mRNA molecules.

The researchers note in their review that genetic variations in HIV-1 may account for differences in the sequences of the Rev-RRE complex, which, in turn affects its potency to enable viral mRNA export from a cell nucleus. Some primary isolates of components from infected cells show differences in Rev-RRE activity and a few studies have observed a correlation between lower Rev-RRE activity and slower progression of clinical disease. Lower Rev-RRE activity has also been associated with the evasion by affected cells from cytotoxic T lymphocyte mediated killing.

The team notes that this HIV-1 Rev-RRE regulatory axis is an understudied mechanism which enables viral adaptation to diverse immune milieus. "There is evidence that this adaptation may play a role in HIV pathogenesis, particularly in immune evasion and HIV latency, but further studies with larger sample sizes are required," concludes Jackson.

Keywords: HIV Rev, HIV Rev Response Element, HIV sequence variation, HIV latency, RNA splicing, post-transcriptional gene regulation.

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