HIV-like gene lies buried in human DNA.

Scientists exploring the evolution of viruses can't dig into the ground for fossils. Instead, virologists can look inward to the genetic code within their own cells for signs of ancient infections.

As much as 1 percent of human DNA consists of genetic fossils of viruses that once inserted their genes into the genomes of human ancestors. While studying one such viral remnant, investigators have found that a virus that infected primates many millions of years ago used a protein with an uncanny resemblance to one employed by the modern killer HIV.

This unexpected finding may force scientists to rewrite their histories of the AIDS virus and similar viruses because they had considered the HIV protein, named Rev, a recent viral innovation, says Bryan R. Cullen of the Howard Hughes Medical Institute at Duke University Medical Center in Durham, N.C. He and his colleagues report their analysis of the Rev-like protein in the Nov. 9 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

Unlike most viral remnants, rendered inactive by the ravages of time, the one studied by Cullen's group retains several genes that can still make proteins, though they can't produce an infectious virus. Scientists believe that 30 million years ago the virus, which they call human endogenous retrovirus K (HERV-K), first infected the germ cells--sperm or eggs--of Old World monkeys whose descendants include the human species.

By entering the germline, the virus forever established itself in every cell of those monkeys' offspring. Such infections probably occurred a few dozen times over the next 25 million years, given that people have more than 50 different copies of HERV-K in their genome, says Cullen.

Generally considered harmless, HERVK lies dormant in most cells. In a few tissues, including the placenta, the genes of the retrovirus produce proteins whose effect is not known. For unexplained reasons, certain tumor cells also exhibit high levels of HERV-K activity.

Several years ago, German researchers studying the genes of HERV-K suggested that one of them encodes a protein similar to the Rev used by the AIDS virus. Rev shuttles a copy of HIV's genetic material out of an infected cell's nucleus, a necessary step in the creation of new viral particles.

Because today only HIV and a few other infectious retroviruses have a Rev protein, scientists theorized that it's a recent development in viral evolution. Consequently, Cullen was initially skeptical that a retrovirus as old as HERV-K produces such a protein. His group, however, has now shown that the HERV-K protein, called c-orf, can indeed bind retroviral genes and ferry them out of the nucleus.

Scientists place HERV-K and HIV in different retroviral families. Cullen's finding suggests that an ancient ancestor of the HIV family picked up its Rev through a genetic swap with HERV-K or a related retrovirus.

Alternatively, notes John M. Coffin of Tufts University School of Medicine in Boston, both may have stolen the ancestral gene for Rev from cells they infected. "Studying [retrovirus remnants] has great potential for illuminating the evolution of all viruses, including HIV," he adds.