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Ancient Virus Sheds Light on AIDS

Genomics and archaeology may seem unrelated, but knowing the genomes of several different animals gives researchers the chance to explore many historical questions. A study of an ancient virus has now revealed how evolutionary events may have left our species more vulnerable to the virus that causes AIDS.

Retroviruses like HIV copy their genetic information during infection and insert it into the DNA of the host they're infecting. It's one way viruses can hide from immune system attack. For some retroviruses (but not HIV), the insertion into the host DNA can be passed down from one generation to the next. Both the chimpanzee and the gorilla came to have more than 100 copies of an ancient retrovirus called Pan troglodytes endogenous retrovirus (PtERV1) in their genomes. Humans, however, have none. Researchers believe that this virus was active 3 to 4 million years ago, after the evolutionary separation of chimpanzees and humans. Dr. Michael Emerman at the Fred Hutchinson Cancer Research Center and his colleagues wondered why our sister species acquired so many copies of this retrovirus while we have none.

The researchers, in work partly funded by NIH's ×îÐÂÂ鶹ÊÓƵ Institute of Allergy and Infectious Diseases (NIAID), turned to an immune system protein called TRIM5α, which binds directly to an incoming retrovirus to mark it for destruction. The researchers hypothesized that TRIM5α may have protected early humans from PtERV1.

PtERV1 is now extinct; all its genomic copies have been inactivated by accumulated mutations. However, as the researchers reported in the June 22, 2007, issue of Science, the many copies of PtERV1 in the chimpanzee genome allowed them to reconstruct the ancestral sequence of the retrovirus's core protein, which is targeted by TRIM5α. The researchers then tested how well human TRIM5α can restrict PtERV1 by engineering cells to make TRIM5α. Those making human TRIM5α turned out to be 100 times more resistant to infection by the reconstructed retrovirus.

While human TRIM5α does seem to protect against PtERV1, it isn't very effective against another retrovirus, HIV-1. The researchers found, however, that one key change in human TRIM5α taken from a human-chimp-gorilla ancestor improved the protein's ability to restrict HIV-1. At the same time, the change rendered it ineffective against PtERV1. They next tested a panel of TRIM5α genes from other primates and found that each TRIM5α efficiently restricted either PtERV1 or HIV-1, but none could restrict both.

Although the researchers can't rule out the possibility that PtERV1 never infected human ancestors in the first place, these results suggest that modern humans descended from ancestors whose version of TRIM5α gave them protection against PtERV1. This intrinsic immunity would have effectively neutralized the retrovirus, explaining why we now find no traces of it in the human genome. At the same time, these experiments reveal a possible evolutionary trade-off: the same gene that may have protected us from PtERV1 now contributes to our vulnerability to HIV-1.

— by Harrison Wein