Viral Stowaway

A virtually intact retrovirus has been found trapped in the human genome. The virus sports a full complement of genes, but a key mutation probably prevents it from infecting the rest of the genome or other cells. The finding, reported in the March Nature Genetics, raises the odds that active retroviruses may lurk in our chromosomes--and may even slip out on occasion to possibly cause disease-promoting alternations in human DNA.

About 1% of the human genome is filled with a haphazard collection of DNA from retroviruses, whose genetic material long ago weaseled into the chromosomes of eggs or sperm and were passed on to subsequent generations. Although active retroviruses have been found in the chromosomes of mice and other animals, retroviral genes in people are scattered throughout the genome and are not known to be able to reassemble themselves into functioning viruses.

Over the past several years, however, Eckart Meese and Jens Mayer of University of the Saar in Hamburg, Germany, and a few other teams have discovered several functional retroviral genes belonging to a group called HERV-K. Another group in Germany has even found HERV-K retroviral particles in cells grown from testicular tumors, and their preliminary work indicates that some retroviral genes increase their activity in precancerous reproductive tissue. These findings made Meese and Mayer even more eager to search for a full-fledged retrovirus, called a provirus, in the human genome.

The team began by screening chromosome 7--known to have retroviral genes--to pinpoint functional genes called gag and env. Next they determined that these genes were in between nearly identical stretches of repetitive DNA called long terminal repeats. Two other retroviral genes were also sandwiched between these repeats, enough for a complete retrovirus (retroviruses need at least four genes to make the bare minimum complement of proteins). But one--the gene for reverse transcriptase, which converts viral RNA to the DNA that can be incorporated into the host cell's genome as a provirus--was mutated.

This is the first time a virtually complete sequence of a provirus has been found within a human chromosome, says Dixie Mager, a molecular geneticist at the British Columbia Cancer Research Center's Terry Fox Laboratory in Vancouver. And because intact reverse transcriptase genes exist elsewhere in the genome, the provirus might be able to use the proteins made from these genes to help it produce mature virus. However, "whether it can be infectious has not been shown," says virologist Jonas Blomberg of the University of Uppsala in Sweden.