Dr. Michael Emerman to give Bernard Fields lecture at CROI

Fred Hutchinson Cancer Research Center HIV researcher Dr. Michael Emerman will give the Bernard Fields Lecture on Sunday, March 8, at this year’s Conference on Retroviruses and Opportunistic Infections, held this year in Boston. The Fields Lecture, named for renowned virologist Dr. Bernard Fields, is given during the opening session of CROI by a basic scientist recognized for his or her contributions to virology. Due to the Hutch’s recently implemented restrictions on work-related travel during the outbreak of SARS-CoV-2 in the Seattle area, Emerman will present his lecture remotely.

Emerman studies how HIV became a human pandemic pathogen as it evolved from a virus that infects Old World primates to a chimpanzee infection to a deadly infection in humans that raced around the world in a decade. He argues that understanding how primates evolved to escape related viruses and the immunological weak spots HIV exploited to infect us will point the way toward anti-HIV therapies, and possibly even a cure.

“I'm going to use these evolutionary lessons of the origins of HIV-1 to talk about how we can use these lessons to effect HIV cure where we're not going to wait for millions of years,” he said.

HIV’s ancient origins

Emerman studies HIV-1, the most common and pathogenic form of HIV, the major global pandemic of the last 35 years. HIV arose from a simian immunodeficiency virus, or SIV, that jumped from a chimp to a human about 100 years ago. Various SIV strains have been circulating in other Old World monkeys in Africa, known as simians, for a long time.

When scientists first made the connection between HIV and SIVs, they thought the simian-infecting variants were a few hundred or thousand years old. Further research pushed this to 10,000 years, then 100,000 years. Then Emerman’s group calculated that these estimates were also off — by an order of magnitude. Instead, their work showed that these viruses are five to 10 million years old. This helps explain why, unlike HIV in humans, SIVs don’t cause acute disease in monkeys, their natural hosts.

“Our studies imply is that over these millions of years, primates in Africa have evolved to be tolerant of their viruses,” Emerman said.

Lessons from evolution

According to work from his lab and others, many of these changes occurred in genes in the innate immune system, the branch of our immune system that mounts rapid responses to overarching viral and bacterial characteristics. But many of the changes that allowed primates and SIVs to achieve balance didn’t occur in humans, leaving “holes” in our immune system that HIV was able to slip through.

“The virus we have is not the virus that our immune system is optimized for,” Emerman said.

But even as HIV exploited our vulnerabilities, we may be able to exploit its weak points. Virologists like Emerman, who think in evolutionary terms, talk of trade-offs: becoming good at one thing usually means becoming worse at another. A common example used by Paul Turner of Yale University compares cheetahs to lions: To become swift enough to take down an impala, cheetahs traded the size and strength needed to kill a zebra. Lions, which are large and strong enough to kill a zebra, cannot run fast enough to prey on an impala.

As HIV changed to jump from monkeys to chimps to humans, it likely made a similar trade-off because genes were lost or changed in the process, Emerman said.

“We want to identify the genetic vulnerabilities of HIV due to these changes,” he said.

Basic science points the way

We don’t have the luxury of waiting several million years to evolve toward a détente with HIV. But basic research like Emerman’s “tells us where to look [for genetic vulnerabilities],” he said.

If we can better understand how simians evolved to bypass the disease-causing effects of SIV, we may be able to develop HIV therapies that mimic these in humans by making the human innate immune system work better against HIV, Emerman said.

This could include developing small molecules that make our innate immune factors work better, or by focusing HIV cure efforts on the crucial population of cells that express these genes and are most important for staving off infection. Emerman and Hutch colleague Dr. Harmit Malik have also experimented with using evolutionary insights to improve the activity of a key antiviral gene.

“The idea is we can learn these things from evolution, and there are suggestions of ways forward,” he said.