Satish, a self-described curiosity junkie, wasn’t always interested in HIV. As a freshman at the University of Arizona, he had romantic visions of becoming a stargazing astronomer, but was soon frustrated by the math courses and by a basic fact of life in astronomy: the light from stars is millions of years old by the time it reaches us. It’s all ancient history! He made a switch to evolutionary biology, only to run into the same problem. Says Satish, “I was always frustrated by the fact that evolution in larger animals occurs on glacial timescales. You can never really watch a marine mammal evolve from a terrestrial ungulate. But then I started reading about host/virus coevolution — and that was my light-bulb moment!” Today, Satish has found his calling studying HIV’s lightning-fast evolution using tools that were originally developed to unravel the history of much larger, slower-evolving plants and animals.
From a biological perspective, there’s not much difference between an invasive species running wild in a hospitable, island ecosystem and an HIV infecting a new host, other than the sizes and timescales involved. In the case of sexual transmission, an HIV infection begins with a single virus or a few closely related virus particles, which then multiply exponentially, without competition or ecological checks. As it multiplies, it accumulates mutations and evolves, just as invasive species do. Within days or weeks, the host’s blood is packed with virus copies, and the virus will have invaded different “niches” in the body — from the spleen to the central nervous system. Once the body’s immune response kicks in, levels of virus in the blood will drop again — but at that point the virus has already incorporated its genome into cells all over the body.
Satish was intrigued by the possibility that, as the virus invades different organs and tissues, it evolves in predictable ways — and that its predictability might allow us to overcome one of the biggest barriers to vaccine development: HIV’s extremely high levels of genetic variation.