Published online 21 June 2007 | Nature | doi:10.1038/news070618-15
Corrected online: 26 June 2007

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Ancient disease resistance made us vulnerable to HIV

Early immune resistance may have helped to set stage for modern pandemic.

On the defense: our immune system has an extra barrier not found in chimps.On the defense: our immune system has an extra barrier not found in chimps.Narelle Towie/NT

Humans may be susceptible to infection by HIV because our ancient ancestors evolved resistance to another virus.

That's the conclusion reached by researchers who have compared our own genome sequence with that of apes, in search of signs of old viral attacks. The team wondered whether chimps had been battered by a virus that humans had evolved a resistance to, and whether that resistance might shed some light on our modern susceptibility to other viruses. Their hunch was right.

The DNA of our closest evolutionary relatives is riddled with the hallmarks of a now-extinct virus called PtERV1. This virus probably infected chimpanzees and other apes around four million years ago — after chimps' evolutionary split from humans. Chimps were badly hit by the virus. But humans, it seems, could fight it off. Unfortunately, the defensive protein that protects against PtERV1 seems to increase our cells' susceptibility to HIV attack, report Michael Emerman and his colleagues at the Fred Hutchinson Cancer Research Center in Seattle.

PtERV1, like HIV, is a 'retrovirus' — it contains RNA that is converted into DNA within the host cell and then inserted into the host genome. Throughout evolution, such viruses leave a legacy as their DNA is passed on from generation to generation, ultimately becoming present in the entire host population. Roughly 8% of human DNA is made up of these viral leftovers.

It was already known that the chimpanzee genome contains around 130 copies of DNA sequences from PtERV1. But Emerman and his team report in this week's Science1 that not one copy of this viral DNA has been incorporated into the human genome, meaning that something must have fought it off.

Single defence

Emerman and his colleagues used the chimpanzee DNA to reconstruct part of the virus in the lab. They then used this to try to infect feline cells in culture, to which a human protein called TRIM5alpha had been added. This protein prevented the virus from entering the cells. Without it, the cells were vulnerable to the reconstructed virus; but they were also less susceptible to infection by HIV.

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This immune strategy must have carried an evolutionary advantage millions of years ago, Emerman says, "The most obvious benefit is that this protected some humans from disease." But he adds that "we don't really know anything about what sort of disease PtERV1 might have caused."

Unfortunately, the discovery does not hold much promise for efforts to find a vaccine against HIV/AIDS, says Emerman. "I do not see much insight of this work into vaccines, although maybe others can," he says. "I see this work more along the lines of understanding human history by uncovering the past — sort of like archaeology or palaeontology."

What the work does do is spotlight how the human immune system came to be the way it is today. "Our host defence genes have been shaped by a long history of genetic conflict with ancient viruses. If we want to understand why our defences are the way they are, the answers inevitably lie in these ancient viruses, more so than in the ones that have affected us only recently," says Emerman.

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Fred Hutchinson Cancer Research Center

Corrected:

CORRECTION: The original article contained a number of inaccuracies which have now been corrected. The researchers are not geneticists but virologists and evolutionary biologists. The discovery of PtERV1 DNA in the chimpanzee genome was made previously, as now described. The cells used in the study were feline cells with added human protein, not human cells. And the TRIM5alpha protein does not represent the immune system’s only defence against HIV infection.
  • References

    1. Kaiser S. M., Malik H. S.& Emerman M. Science, 316. 1756 - 1758 (2007).