Africa: Ancient Resistance 'Left US HIV Vulnerable'

SciDev.Net (London)

22 June 2007
Posted to the web 22 June 2007

Xu Jing And Jia Hepeng
Beijing

The HIV virus (green) infecting a white blood cell.

A new study reveals that a molecular weapon once used by humans to fend off infection by an ancient virus might now be making them more susceptible to HIV-1, the virus that causes AIDS.

The study, published today in Science (22 June), may offer new insight into the viral mechanisms underlying the modern HIV pandemic, according to researchers at the Fred Hutchinson Cancer Research Centre in Seattle, United States.

During their investigation of the chimpanzee genome, the researchers noticed that genes belonging to a now-extinct virus called PtERV1 (Pan troglodytes endogenous retrovirus-1) were incorporated into the chimp's genetic code.

The retrovirus -- part of a virus family that includes HIV -- probably inserted a DNA copy of itself into the germ line of its chimpanzee host some 3-4 million years ago and has been passed down from one generation to the next.

The team found no such viral genes present in the human genome, indicating that modern human beings are not infected by the PtERV1 virus.

"[Infection by] this virus is a battle that humans have already won. Humans are not susceptible to it and have probably been resistant throughout millennia," said corresponding author Michael Emerman.

Using the viral segments from the chimpanzee genome to reconstruct the core part of the PtERV1 virus, Emerman and colleagues found that a human version of an immune protein known as TRIM5a was able to inactivate the resurrected viral remnant.

But TRIM5a could not stop infection by retroviruses that currently infect humans, such as HIV-1.

The researchers tested different versions of the TRIM5a protein from various primates and found that those able to inactivate the PtERV1 virus were incapable of inactivating HIV-1, and vice versa.

So, say the researchers, it is possible that evolutionary changes that occurred in this protective protein as a result of humans developing resistance to one virus long ago have now rendered the protein ineffective against another type of retrovirus -- HIV.

"In the end, [the TRIM5a protein's ability to fight PtERV1] drove human evolution to be more susceptible to HIV," says Emerman.

Zhang Linqi, director of the AIDS Research Center at Beijing-based Peking Union Medical College, says that the research highlights a possible interactive mechanism between virus and cells that could lead to better understanding of the process of HIV infection.

"But it is hard to fully understand HIV infection through a single gene, since viral infection of the human body is a comprehensive process related to various parts of human genome," Zhang told SciDev.Net.

Link to full article in Science

Reference: Science 316, 1756-1758 (2007)

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