Discovery of virus in lemur could shed light on AIDS

The tiny gray mouse lemur is found only in Madagascar.

The genome of a squirrel-sized, saucer-eyed lemur from Madagascar may help scientists understand how HIV-like viruses coevolved with primates, according to research published online Dec. 1 in the Proceedings of the National Academy of Sciences. The findings could provide insight into why non-human primates don't get AIDS and lead to treatments for humans.

Scientists have long believed that lentiviruses—the family of viruses that includes HIV—started infecting primates within the past million years. In fact, said Rob Gifford, PhD, former postdoctoral researcher in infectious diseases and the study's lead author, lentiviruses may have existed in ancestral primates as long as 85 million years ago.

A type of retrovirus, lentiviruses replicate by inserting their RNA into a cell's DNA. Some retroviruses infect cells that mature into sperm or eggs, incorporating viral DNA into the host's genome. No one knew lentiviruses could be inherited this way until last year, when Gifford discovered Rabbit Endogenous Lentivirus type K among the DNA of the European rabbit. "It allows us to put a timeline on the evolution of primate lentiviruses," said Robert Shafer, MD, associate professor of infectious diseases and geographic medicine and the paper's senior author.

Gifford began computer-based screening of the DNA of 21 primates. He searched the genome sequencing of each species for strings of nucleotides that matched the modern lentivirus genome and found one lurking in the DNA of the tiny gray mouse lemur.

Ancestors of this lemur colonized Madagascar about 75 million years ago, and since then, lemurs and their lentivirus-carrying cousins on the African mainland have been evolving separately. The last of the land bridges between Madagascar and Africa disappeared 14 million years ago, suggesting that lentiviruses are likely at least that old. Four hundred kilometers of ocean divide the two branches of primates, limiting the opportunities to swap germs.

Estimates of the age of this lentivirus, called pSIVgml, go as far back as 85 million years, when the primate family that includes lemurs split from the evolutionary branch that yielded monkeys, apes and humans. "Lentiviruses could be very ancient indeed," Gifford said.

Gifford remains cautious about overestimating the virus's age, warning that the virus could have been spread within the last 14 million years by something that could cross the ocean, such as a bat. But Shafer said that sort of cross-species transmission is unlikely, becauce the leap from primate to bat and back would be difficult for a lentivirus to make.

Gifford's find suggests lentiviruses could be discovered elsewhere, perhaps in Asian and New World monkeys. "As far as we're aware, nobody's really looked that hard," he said. He is one of the few researchers using genome databases to search for retroviruses.

Finding widespread lentivirus-primate interaction might open doors for HIV/AIDS research. Primates infected with the simian version of HIV are protected from developing AIDS by several genes which code for proteins in the immune system that slow or block retroviral reproduction. Previous research suggests these genes evolved in response to millions of years of retrovirus infection.

Until now, scientists thought lentiviruses were too young to have participated in this evolutionary back-and-forth. But if Gifford and his colleagues find more evidence that lentiviruses and primates have been in each other's genetic business for many millions of years, they could turn that assumption on its head. New insights about the evolution of ancient innate immune defenses against retroviruses could lead to HIV treatments or vaccines.

The research "raises interesting questions about how mammals have dealt with these types of viruses over a minimum of 14 million years, what kind of defenses they have developed, and why some mammal species have lost these viruses," said Beatrice Hahn, PhD, a professor at the University of Alabama-Birmingham who studies human retroviruses. She hopes to see more research on lentiviruses in mammal genomes. "This is molecular archaeology," she said. "There may be a lot of gold in these sequences that hasn't been mined yet."

Gifford and Shafer conducted this study with researchers from the Imperial College of London and the Institute for Emergent Infections at the James Martin 21st Century School at Oxford. Funding was provided by the National Institute of Allergy and Infectious Diseases and the James Martin 21st Century School.

Stephanie Pappas is an intern in the medical school's Office of Communication & Public Affairs.