Understanding HIV by delving into our past
Harmit Malik and Michael Emerman, biologists
When we think about deadly viruses, evolutionary biologist Harmit Malik explains, we need to understand that their complexity and ferocity has been bred through tens of millions of years of tugging and pulling against the human race.
"In this genetic conflict, either the host is winning or the virus is winning," Malik said, pointing to the roughly 8 percent of the human genome that is made up of old retroviruses that we carry inside of us like bits of shrapnel from ancient wars.
Today, we face HIV. It crossed over from chimpanzees to humans within the last 100 years, so far killing 25 million people and infecting twice that many. Why does it kill us and not chimpanzees, which are easily infected by HIV but not sickened by it?
Malik and Michael Emerman, a molecular biologist, have pondered such questions for a long time. Most recently, their collaboration has yielded important insights into the evolutionary struggle between viruses and humans. Ultimately, they hope their research may lead to new drugs to fight HIV.
In one of their most startling collaborations, their labs used the power of modern computers and DNA technology to assemble a new version of an extinct retrovirus known as Pan troglodytes endogenous retrovirus (PtERV), which infected chimps and gorillas-but not humans-4 million years ago. By reassembling the retrovirus in such a way that it could reproduce only once, Malik and Emerman found that a human protein known as TRIM5? easily defeated PtERV. Every primate has a version of the TRIM5? protein. In the rhesus monkey, for example, it kills HIV.
Malik and Emerman also modified the human TRIM5? protein to resemble a version present in the ancestors of humans, chimpanzees and gorillas, and found that it no longer protected against the PtERV. By modifying TRIM5?, they also discovered that one version protected against HIV but not PtERV. In another modification, it did the opposite.
Such polar opposites, they agree, are the result of evolution. Because our TRIM5? protein evolved to fight other retroviruses, it likely left us vulnerable to HIV, they say. Is it possible to reproduce a drug that behaves like a chimp's TRIM5? does against HIV, or change the human version ever so slightly so it kills HIV? These are the kinds of challenges that Emerman and Malik ponder. The two agree that studying, and in some cases reconstructing, ancient viruses is not a trivial matter.
In this arms race that's millions of years old, it pays to understand the enemy, Malik said.
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