Speed of HIV change leaves immune system reeling

An impressive study of the startling rate at which HIV can evolve took firstprize in the 25th annual Whittaker Awards at NUI …

An impressive study of the startling rate at which HIV can evolve took firstprize in the 25th annual Whittaker Awards at NUI Maynooth. Dick Ahlstrom reports.

HIV evolves so rapidly that it leaves our powerful immune system in the dust according to a researcher who has managed to measure just how quickly the AIDS virus can change. Details of research into the virus conducted by third-year bioinformatics student Aisling Ní Ruairc was presented during the 25th annual Whittaker Awards, an event organised by the Biology Society at NUI Maynooth. She claimed the top award, including €600 in prizes during last week's event with a tour de force study comparing the "adaptive evolution" of two forms of HIV and its simian equivalent, SIV.

She sought and received an eight-week funding award from the Health Research Board to pursue the work last summer, but the project actually stretched to about 12 months, says Ní Ruairc. Her focus was on lentiviruses, a group that includes the notorious HIV.

"The reason I chose lentiviruses is because they are RNA viruses. They are very small but are so destructive to humans," she says. "I was trying to determine adaptive evolution, that is the changes in an organism's genome that are beneficial to that organism."

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HIV is a recognised master at adaptive evolution, so much so that our immune systems just can't keep up, says Ní Ruairc. "It is leaving our immune systems for dust."

She decided to see just how variable her target lentiviruses, HIV1, HIV2 and SIV actually were. While she expected to see a high level of evolution across a collection of viral genomes, she did uncover a few surprises.

She got full genomes for more than 100 forms of HIV from the Los Alamos laboratories in the US, but selected 21 each of the three viruses for her comparisons. Working with supervisor Dr James McInerney, she devised a way to study variability across these collections, writing two purpose-built computer programmes to facilitate this.

The approach did not work well for SIV but gave very good results with the HIV viruses. The analysis was highly complex despite the comparatively small viral genome involved, just three main genes encapsulated in a genome about 9,000 to 10,000 bases long.

It involved creating window-like views of the 21 genome collections, looking at matching lengths of RNA about 2,000 bases long. Variability was measured in this window and then the window view moved along the genome by one base. The analysis was repeated and the view notched ahead step by step, eventually giving about 10,000 window views for each of the virus collections.

"We could track variability which is equivalent to the rate of evolution," says Ní Ruairc. Not surprisingly the genes associated with HIV envelope proteins showed a high degree of evolution, testimony to the challenge faced by our immune response.

Another gene, known as Gag, also displayed exceptional variability in HIV1, however. "It was totally unexpected," says Ní Ruaric, and she hopes to look into reasons for this in ongoing research next summer, provided the funding can be found.

Gag is involved in structural aspects of the virus and it is not clear why HIV 1 exhibits such variability. HIV 1 infects more people than HIV 2 and perhaps Gag variability assists its infectivity, she suggests. "The envelope interacts with the immune system. What is really interesting is Gag is another structural gene that evolves quickly in HIV. Does it help the envelope protein?" she asks. Her finding shows that HIV 1 displays a different evolutionary strategy to HIV 2.

The Whittaker Awards are at this stage an institution at Maynooth. They were founded 25 years ago by the then newly arrived professor of biology, Prof Peter Whittaker, and the then head of the Biology Society, now DIT lecturer, Dr Rita Dempsey.

"It was really to get students into the idea of developing their presentation skills," explains Dempsey. "It was also entertainment for the Biology Society."

The Society hadn't a name for the event but hit on the idea of calling them the Whittaker Awards after the new professor. Whittaker would have none of it but the Society was determined. "We twisted his arm and we prevailed," Dempsey said. "I am delighted it has lasted so long," she added. And the rest, as they say, is history.