22 June 2007

Ancient clue to HIV

Humans' distant ancestors beat back a now-extinct virus 4 million years ago, but that victory left the species vulnerable to HIV today, scientists believe.

Humans' distant ancestors beat back a now-extinct virus 4 million years ago, but that victory left the species vulnerable to HIV today, scientists believe.

The finding may also explain why chimpanzees, gorillas and other primates resist infection with the virus that causes Aids, while humans are much more easily infected.

The difference lies in a human gene called TRIM5alpha, which, in lab experiments, effectively blocked infection from a reconstructed portion of the ancient retrovirus, called PtERV1. That virus probably flourished 4 million or 5 million years ago but is extinct today.

Writing in the June 22 issue of Science, the researchers say PtERV1 left behind telltale traces of its DNA inside the genomes of many primates - with the notable exception of humans, suggesting it never gained a foothold there.

What makes us different
In fact, when geneticists first compared the genomes of humans against those of chimps, "the biggest difference is the presence [in nonhuman primates] of this virus, PtERV1," said study senior author Michael Emerman, a member of the Human Biology and Basic Sciences divisions at the Fred Hutchinson Cancer Research Centre, in Seattle.

"There are about 130 copies in the genomes of chimps and gorillas, and maybe other primates, but it's not present at all in the genome of humans," Emerman said.

That could mean one of two things, he said: Either the ancestors of Homo sapiens already carried the TRIM5alpha gene and couldn't be infected by PtERV1, or PtERV1 wiped out all but a few individuals who were lucky enough to carry the gene. Those individuals might then have passed the gene on through their progeny, right up to the humans of today.

A dark legacy
However, that early antiviral victory may have a darker legacy.

The experts found that various primate species carry slightly different versions of TRIM5alpha, one of a class of infection-blocking genes called "cellular restriction factors." In the case of Homo sapiens, the gene's ability to block infection against PtERV1 does not seem to extend to another dangerous retrovirus, HIV.

"We know that the human version of TRIM5alpha isn't good at all against HIV," Emerman said.

On the other hand, the TRIM5alpha found in chimps and gorillas appears to be very effective in denying HIV access to cells. It probably wasn't much good against PtERV1, however.

An either/or situation
This type of "either/or" situation often happens in genetics, Emerman said. Genes change so that species "get better at something - but they get worse at something else," he said.

The end result in this case is that "the human type of TRIM5alpha does not restrict HIV, and yet the TRIM5alpha in other primates can restrict HIV infection," explained Rowena Johnston, vice president for research at the Foundation for Aids Research (amfAR) in New York City. "The critical question is, what do they have that we don't have?" she said.

She and Emerman agreed that the Hutchinson discovery isn't of immediate practical benefit to the fight against Aids. But Johnston said research focused on cellular restriction factors such as TRIM5alpha remains "one of the most promising and interesting areas of research that we have going on in the HIV world right now."

"Is there a way for us to be able to use that information to make our TRIM5alpha more potent against HIV, or at least to work out how it is that TRIM5alpha works in other animals?" she asked. "Or, to see if we can come up with some kind of mimic that would do something similar in humans?"

Advances along those lines are likely to be a "long way off," Johnston cautioned.

"What we are really talking about here are millions of years of human evolutionary history that's made us how we are today," she said. "As the paper says, we've ended up with this trade-off. We have this great protection against PtERV1, and none of the protection against HIV." – (HealthDayNews)

Read more:
HIV/Aids Centre

June 2007


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