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Fossil virus reveals clues to today's HIV pandemic

Scientists explain how innate human immunity to ancient retrovirus PtERV1 increases our vulnerability to HIV infection

July 1, 2007
 Dr. Michael Emerman and Shari Kaiser

Dr. Michael Emerman and graduate student Shari Kaiser employed the emerging field of paleovirology, the study of ancient viruses, to gain insight into human susceptibility to modern-day HIV infection. They found innate immunity to PtERV1 may have made humans more vulnerable to HIV.

Photo by Dean Forbes

Ironically, human resistance to a retrovirus that infected chimpanzees and other nonhuman primates 4 million years ago may be at least partially responsible for the susceptibility of humans to HIV infection today.


"This ancient virus is a battle that humans have already won," said senior author Dr. Michael Emerman, of the Center's Human Biology and Basic Sciences divisions. "Humans are not susceptible to it and have probably been resistant throughout millennia. However, we found that during primate evolution, this innate immunity to one virus may have made us more vulnerable to HIV."

Evidence of human immunity to this ancient retrovirus first emerged with the sequencing of the chimpanzee genome. "When the chimp genome was sequenced, a team of scientists at the University of Washington led by Dr. Evan Eichler found the largest difference overall between the chimp and human genomes was the presence or absence of PtERV1," Emerman said. "Chimps have 130 copies of PtERV1 and humans have none."


Innate immunity

Innate protection against PtERV1 in humans could be due, the researchers believe, to the presence of an ancient, rapidly evolving antiviral defense gene called TRIM5α, which produces a protein that binds to and destroys the virus before it can replicate within the body.

"We know that PtERV1 infected chimps, gorillas and old-world monkeys 4 million years ago but left no traces of having infected humans. Our theory is that this is because humans had this innate viral-defense system," Emerman said.

To test their hypothesis, Emerman and co-authors Dr. Harmit Malik, an evolutionary biologist in the Center's Basic Sciences Division, and Shari Kaiser, a graduate student in Emerman's laboratory, used DNA sequences from the chimp genome to reconstruct a small part of the PtERV1 virus.

Creating 'ancestral' sequence

They reassembled about one-fifth of the virus by taking dozens of PtERV1 sequences and aligning them to create an "ancestral" sequence, teasing out areas of commonality between them. They then used this information to make a partial viral genome. The researchers debilitated the viral segment during reconstruction, enabling only one round of infection in cells. Working with cells in the laboratory, the researchers found that the human antiviral protein TRIM5α effectively neutralizes this extinct retrovirus, which never successfully fixed into the human genome.




Emerging field of research

In fact, the name for this emerging area of research, which seeks to better understand modern infections by studying ancient viruses, is "paleovirology."


National Institutes of Health grants to Emerman, a Searle Scholar Award to Malik and a National Science Foundation graduate fellowship to Kaiser supported the study.


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