Spotlight on Harmit Malik

Understanding HIV by Delving Into Our Past

Harmit Malik, Biologist

When we strive to conquer deadly viruses, evolutionary biologist Dr. Harmit Malik believes 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?

Dr. Harmit Malik
Dr. Harmit Malik in his lab at Fred Hutch. Robert Hood / Fred Hutch

Malik has pondered such questions for a long time. Most recently, his research has yielded important insights into the evolutionary struggle between viruses and humans. Ultimately, Malik hopes this research may lead to new drugs to fight HIV.

Malik’s lab collaborated with other Hutchinson Center researchers to use the power of modern computers and DNA technology. The team assembled 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 colleagues found that a human protein known as TRIM5alpha easily defeated PtERV. Every primate has a version of the TRIM5alpha protein. In the rhesus monkey, for example, it kills HIV.

Malik has also helped modify the human TRIM5alpha protein to resemble a version present in the ancestors of humans, chimpanzees and gorillas, and found that it no longer protected against the PtERV. Using the modified TRIM5alpha, Malik discovered that one version protected against HIV but not PtERV. In another modification, it did the opposite.

Such polar opposites, Malik and colleagues agree, are the result of evolution. Because the human TRIM5alpha protein evolved to fight other retroviruses, it likely left us vulnerable to HIV, the research shows. Is it possible to reproduce a drug that behaves like a chimp's TRIM5alpha does against HIV, or change the human version ever so slightly so it kills HIV? These are the kinds of challenges that Malik and his scientific collaborators ponder. Malik and his colleagues say 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.


Researcher News

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Grant King named a 2023 Damon Runyon Fellow Malik Lab postdoc will study how cells handle extra-chromosomal DNA August 16, 2023
Struggle between sex chromosomes underlies evolutionary paradox DNA-packaging protamine genes evolve rapidly to stay ahead in battle between ‘selfish’ genetic elements and the rest of the genome February 10, 2023
'Microprotein' researcher Maria Toro Moreno is named a Hanna Gray Fellow Postdoc wins prestigious award from the Howard Hughes Medical Institute August 24, 2022
Drs. Harmit Malik and Steve Henikoff elected to American Academy of Arts and Sciences Election honors scientists’ contributions to understanding of fundamental biology April 28, 2022