A French researcher joins a UCD research team to study how HIV infects cells so efficiently, writes Dr Claire O'Connell
HIV, the Aids virus, looks after its own needs by hijacking an infected cell's biochemical machinery. But now scientists are turning the tables on HIV by recruiting a natural cellular process called RNA interference (RNAi) to find out more about how the virus works.
"RNA interference happens in many organisms and provides a way of regulating gene expression," explains Dr Jean-Marc Jacqué, who is an assistant professor at the University of Massachusetts Medical School. He uses RNAi to look at how HIV infects cells, and he will take up a new research post at University College Dublin (UCD) next week.
In cells, segments of messenger RNA (ribonucleic acid) carry temporary instructions from genes to the cell, effectively giving the cell a recipe for building proteins.
In RNAi, small strands of interfering RNA scramble this process, telling the cell to destroy specific stretches of messenger RNA. This means the cell's protein building machinery doesn't get those instructions, and those genes are effectively silenced.
RNAi acts as a defence mechanism in plants and it also plays a role in the development of roundworm and insect species. When studies showed the technique could be applied to mammalian cells, Dr Jacqué's lab decided to investigate. "We said this is very powerful, it's something that has been used by mother nature for a long time, so let's try it on HIV and see what happens."
So they designed synthetic strands of small interfering RNA to block viral RNA. When they administered the interfering RNAs to immune cells called lymphocytes, HIV's ability to infect those cells was reduced.
Their research, which was published in the prestigious journal Nature, contributed to Science magazine hailing RNAi as the scientific "breakthrough of the year" in 2002.
While some companies are now trying to develop RNAi as a potential therapeutic approach, Dr Jacqué says his lab applies the technique mainly to work out molecular pathways of HIV infection in the cell. "It's a very powerful tool to knock down a gene within a cell and see what happens."
At UCD, Dr Jacqué will continue to use RNAi to look at how HIV gains access to the host cell's DNA machinery in order to make copies of itself and continue an infection. Of particular interest is how HIV manages to get into the cell's nucleus, where the cell's own DNA is held. Most viruses can do this only when the cell is dividing because the protective nuclear envelope breaks down. But HIV can get across the nuclear envelope even in non-dividing cells of the immune system such as macrophages.
From his most recent research in the US, Dr Jacqué has identified nuclear proteins that appear to help HIV entry into the nuclei of macrophages. He plans to continue this work at UCD. "I'm going up step by step, trying to peel off every single layer to see what happens and how it works - what is the mechanism of HIV entry, which proteins of HIV interact with cellular proteins, if it can be bypassed and if you can block it with drugs."
Dr Jacqué's appointment is part of an ongoing strategy to develop UCD as an international centre of excellence in infectious diseases research, says Prof William Hall, director of the Centre for Research in Infectious Diseases.
Prof Hall adds that Dr Jacqué's research into HIV infectivity will complement other programmes at UCD's School of Medicine and Medical Science and the National Virus Reference Laboratory. These include basic research and monitoring of retroviruses and a Health Research Board-funded project led by Prof Bill Powderly to establish a Dublin HIV cohort that will facilitate clinical trials.