Your work has revealed that HIV evolves over the course of infection and becomes more pathogenic than it started. Why is that?
The quick answer is we don’t know. What we think happens is that HIV is escaping the immune response and that’s why it’s evolving. What’s not clear is whether enhanced virulence is an unwanted consequence of immune escape or whether there’s actually a positive selection for those more virulent
viruses. One thing that might lead to selection is the virus being able to find new target cells as it depletes T-cells in the host, but no one’s been able to show that pathway of evolution directly.
You’ve also focused a lot of effort on the subject of re-infection with HIV, also known as superinfection. Why is it a concern?
Re-infection describes a situation in which a person becomes infected from one source partner, has an established infection, and then becomes infected from another source partner with another, distinct viral strain of HIV. The reason it’s a concern is because it suggests that the immune response to the first HIV infection is not adequate to protect against another HIV infection. This could imply that the diversity of HIV makes the immune response to one virus not broad enough to protect against another virus or not potent enough and this potentially sets a very high bar for the kind of immune responses you would need to elicit with a vaccine. You’d potentially need to have something that’s better than what any given strain of HIV can naturally induce.
During your graduate study, your research focused on the protist Euglena. How did you make the shift to virology? What spurred you on?
When I was in graduate school I was in a chemistry department and the work was very basic in nature. When I completed my Ph.D., I felt that such very basic, esoteric focus was not going to drive me sufficiently in science, and it drove me to a program in public health at Harvard. While I was there in the early 80’s, HIV was discovered and it was an exciting time to get involved. I’ve continually evolved more and more translational approaches in my work to be able to apply basic science to public health related problems.
Where do you see HIV research in 10 years?
I think this particular year has been pretty exciting for prevention research and there’s been a lot of encouraging news about how to treat people who are HIV negative but at high risk for being infected. It was known that antiviral prophylaxis worked to prevent vertical transmission, but the recent studies also show it works to prevent sexual transmission as well. In the next ten years one of the challenges will be implementing these approaches that worked in these clinical trials that are perhaps hard to generalize. I think we will still be trying to figure out how to make a good HIV immunogen for vaccines, but hopefully we will be on a solid path. Finally, we may also be starting to harness what we’re learning about innate viral factors that block HIV in cells and learning how to mimic those antiviral activities to prevent replication.
If you had to change careers today and you could do anything, what would you do?
I grew up as a working class kid and I never imagined myself being a scientist when I was younger. The aspects of science that I love are the creativity and flexibility and the opportunities to contribute. I think I would still choose science. Two other options might be being an architect or artist – I took art in school – and I always wanted to be a professional basketball player but I’m too old.
What’s your favorite science book?
I don’t really read much science outside my work, but I just read The Immortal Life of Henrietta Lacks and I really enjoyed it. Also, one of my first grad students published a book recently – a lab thriller called Experimental Heart.
What is something about you that most people don’t know?
My first science job out of college was being a quality control person at a pretzel factory. I’d see if the pH was right and I’d see if the bag weighed enough. I grew up in a little town where a lot of pretzels come from, Hanover, Pennsylvania.