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Editor’s note: Although best known as a cancer research center, Fred Hutch also is a hub of HIV research. This is one of a series leading up to World AIDS Day on the breadth of our work, from investigating HIV at a molecular level to searching for a cure to running the world’s largest HIV vaccine clinical trial network.
We are all shaped by our past. It turns out that our viruses are too.
At approximately 100 years old, HIV is a relatively recent arrival on the human virus scene. But its roots stretch back much farther. Understanding where the virus has come from can help us understand where it’s going — and how to stop it — say evolutionary biologists.
HIV’s “ancestors go back many, many millions of years,” said Fred Hutchinson Cancer Research Center virologist Dr. Michael Emerman.
Emerman leads a research team studying the evolutionary events that allowed HIV to come into being. Before HIV was a human virus, its predecessors were shaped by the immune systems of the other primates they infected. And before humans were ever infected with HIV, our immune system and defense proteins were shaped by other, older viruses.
Understanding both sides of that history is key to understanding the virus and why it’s so dangerous to humans, Emerman said.
HIV’s ancient past
HIV arose from a monkey virus known as SIV, or simian immunodeficiency virus, which is approximately 10 million years old. At least 40 different African monkey species carry their own version of SIV, and for the most part, the animals and viruses exist together peacefully because they’ve adapted together over so many years. SIV is far less dangerous to its monkey hosts than HIV is to us.
Sometime in the more recent evolutionary past — between a thousand and 20,000 years ago — an African chimpanzee ate some SIV-infected monkeys and got infected with a super-strain of the monkey virus, known as SIVcpz, which formed from two SIV strains combining and rearranging. This new combination of genes allowed the monkey virus to adapt to the immune system of the chimpanzee.
Then, about a century ago in Central Africa, SIVcpz jumped from chimps to humans and, with a few more changes, morphed into the virus we now know as HIV.
Photo by Robert Hood / Fred Hutch News Service
More than 30 years after scientists discovered HIV as the cause of the then-unfolding AIDS pandemic, there’s much we still don’t understand about the virus. Emerman and his research team study how HIV evolved to adapt to the human immune system, but much of their work is focused on the human and other primate genes that produce proteins that defend — or fail to defend — against the virus.
His laboratory team is conducting a systematic hunt to uncover all the human proteins that can act defensively against HIV. Many of these proteins are known, but Emerman thinks there are more to find and more to understand about those scientists have already discovered. His team is also working to understand variations in these antiviral proteins among people — what might make one person intrinsically more able to fight HIV? Such work could inform HIV cure research by pointing to the gaps in our immune systems cure approaches need to plug, Emerman said.
“We learn how [HIV] adapted to humans. We learn why humans aren’t all equal, so what are the differences in genes between people in the population?” he said. “We learn what factors are missing from humans, so what are the holes in the human innate immune system that other primates do have?”
Along with Fred Hutch evolutionary biologist Dr. Harmit Malik, Emerman is also working on developing “super-restriction factors” — proteins engineered in the lab by optimizing existing antiviral proteins with the hopes of making a protein that’s more powerful against HIV than the ones we already have.
Emerman’s Fred Hutch colleague, evolutionary biologist Dr. Jesse Bloom, is taking a different tack on laboratory manipulations to better understand HIV. Together with Hutch virologist Dr. Julie Overbaugh and doctoral students Hugh Haddox and Adam Dingens, Bloom is creating libraries of mutant HIVs to help predict the virus’s evolutionary future.
Fred Hutch file
In two recent studies, the research team created genetic mutations in HIV to change each single amino acid — the 20 different building blocks of proteins — to every other possible amino acid in the viral protein known as envelope, or Env. The researchers are using that mutant library to ask how different mutations affect HIV’s ability to infect human cells in the lab.
So far, they’ve found that mutations in the region of Env where a type of immune protein known as a broadly neutralizing antibody attaches to the viral protein weaken the virus’s ability to infect cells. That’s good news for HIV vaccine researchers, including those at the Hutch, who are exploring the potential of broadly neutralizing antibodies to prevent HIV infection.
Their goal in this line of research is to predict the evolutionary paths HIV might take in the future — especially in the presence of an HIV vaccine. If researchers can predict whether the virus is likely to mutate away from certain types of immune proteins, they might be able to design better vaccines to stay one step ahead of the virus.
Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Research Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.
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