How to identify latently infected cells is a burning question that keeps Satish going into the lab every morning, but it is just one of many. Satish’s curiosity runs the gamut — from the origin of new infections, to changes in viral diversity that might signal the onset of AIDS, to questions that go much in time, for example, what role the spread of retroviruses might have played in the speciation and extinction of early human lineages. Satish considers this sort of rampant curiosity to be fundamental to our humanity: “The most basic thing about being human is taking a deep interest in the universe around you. All babies are born scientists. You can see them testing their ideas about the world. Unfortunately, lots of people lose that curiosity along the way. I’m lucky to be in a profession that encourages and expresses that basic aspect of human nature — and that lets me do work that has the potential to improve human welfare at the same time.”

When Satish isn’t working in the lab or teaching medical students, he can be found performing rock, funk, and punk-pop around San Francisco. Says Satish, “Science goes hand in hand with art and music. They tickle complementary regions of the brain.” One thing that he loves about working in science is the lifestyle, which offers both intellectual and temporal freedom — and accommodates a few late night gigs!

Discussion and extension questions:

1. In what ways is HIV’s infection of a new person similar to an invasive species arriving on a new island? In what ways are the two scenarios different? Focus on the evolutionary similarities and differences.
2. What challenges does HIV’s level of genetic variation pose for those who hope to prevent, treat, and cure the disease?
3. Advanced: Satish’s phylogenies are based on HIV’s fast-evolving env sequence. This gene helps the virus invade cells. Discuss some pros and cons of using this gene to build phylogenies.
4. Satish was interested in finding a “signature of selection” in semen-derived virus. Explain what this phrase means and how the signature was detected.
5. Other researchers have studied HIV populations in people who are not taking antiretroviral drugs. The phylogenies of these viruses usually show a strong, time-related signal: viruses sampled later in the infection tend to be more closely related to other late-sampled viruses than to early-sampled viruses. Draw a phylogeny that shows what this might look like. Do these results conflict with Satish’s? Explain why or why not.
6. Satish and his colleagues investigated the case of Timothy Ray Brown. They had genetic sequences from Brown’s viral population before his marrow transplant, sequences from viruses that were supposedly detected in Brown after the transplant, sequences from common lab strains of HIV, and sequences from HIV in unrelated individuals. They used these sequences to build phylogenies. Sketch the sort of phylogeny you would expect to see if Brown were completely cured of HIV and contamination was to blame for detecting HIV in Brown’s body. Sketch the sort of phylogeny you would expect to see if Brown were not completely cured of HIV and the results were not spurious.