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Hijacking Genetic Hijackers

Interfering with the protein production systems of viruses holds potential for the control of a variety of diseases, and an Otago PhD student, Julie Horsfield, is attempting to do just that.

Ribosomes in plant and animal cells translate genes encoded on messenger RNA into proteins. This process is normally very accurate, with ribosomes faithfully decoding a single stretch of RNA to produce a single protein. However, some retroviruses are able to subvert the process of translation in order to produce more than one protein from the same stretch of nucleic acid.

This is achieved by a process called ribosomal frameshifting, where the fidelity of the ribosome is compromised so that the messenger RNA is allowed to "slip" along the decoding site of the ribosome. This enables two proteins to be produced, each decoded in a different reading frame. The information needed for frameshifting is contained in the virus's mRNA.

The HIV-1 retrovirus associated with AIDS uses ribosomal frameshifting to produce gag and pol proteins from the same mRNA, in the ratio of about 10 gag to 1 pol. Research suggests that maintaining the correct proportion of viral proteins is essential for the lifecycle of these viruses.

Because the frameshifting strategy is not thought to be used in normal cellular processes, disrupting it could provide a means of controlling such viruses, Horsfield says.

She is looking at a number of viruses, including the HIV-1 virus, the tobacco mosaic virus and the bovine leukmia virus. Horsfield hopes to be able to interfere with the viruses' lifecycles by using antibiotics and drugs known to affect the accuracy of ribosomes in translation. These drugs would potentially upset the critical balance of viral proteins produced by ribosomal frameshifting.

By perturbing the frame-shift mechanism used by such retroviruses, Hors-field's research could lead to a novel approach for interfering with the life cycles of these viruses. The study is being supported by a Health Research Council scholarship.