Protein Mimics Trap HIV Virus in a Cellular Box

Author:  Charley Wang
Institution:  University of Toronto
Date:  December 2007

HIV has killed over 25 million people since its emergence in late 1981. The virus' resilience comes from mutations – there could be thousands of different HIV strains in a single patient, each with their own resistance to treatments. Research teams from the University of Zurich and the University of Washington have potentially developed a new class of drugs to treat the pandemic Human Immunodeficiency Virus

All HIV strains are RNA lentiviruses that attack the same way, regardless of how often they mutate. First, the virus injects viral RNA into the host cell. Then, using viral reverse transcriptase, it creates DNA that is incorporated into the host's own genetic code. This reverse transcription process is error-prone and can leave many mutations. This is one of the main reasons why HIV mutates so rapidly, making it so difficult to treat.

However, this study shows that the mechanism also represents an HIV weak spot. Viral DNA, once copied into the cell nucleus, can not leave and must export RNA molecules in order to have an effect. Since the virus is not native to the cell, the transport process must be carried out by another viral protein, called Rev.

The team, led by Professor John A. Robinson, target Rev binding sites on the viral RNA through the use of a peptide mimetic. These peptides mimic' the structure of a target protein and firmly bind to Rev responsive elements (RRE) on the viral RNA, thereby inhibiting Rev binding. Without Rev, viral RNA cannot leave the host nucleus and the virus is effectively trapped within the host cell and will not be able to cause any further damage.

Previous efforts to find RRE inhibitors have been met with limited success. "Hairpin peptide mimetics are a highly promising new class of drugs," says Dr. Robinson. Mimetics provide one novel way to target drug-resistant strains of HIV as RRE's are a very common feature of the HIV virus.

Whether such mimetic treatment plans will prove effective in the long run remains to be seen. Further research into effectiveness and delivery is currently underway.

Written by Charley Wang

Reviewed by Andrew Wang

Published by Pooja Ghatalia.