Published 27 June 2011

Jonathan Carlson tries to understand how HIV adapts when it is attacked

Yesterday’s opening ceremony was concluded with a panel session that featured Bill Gates, Nobel laureate Ada Yonath, Sandra Chisamba and Jonathan Carlson. Together they discussed how we should deal with threats to global health, such as HIV and malaria, and how young scientists could be stimulated to research these important, but relatively neglected topics.

Jonathan Carlson was part of the panel as a computer scientist working for Microsoft. This doesn’t mean that he is trying to improve Internet Explorer or working on the next iteration of Windows. Quite the contrary. At Microsoft, Jonathan studies how HIV adapts to its host. Earlier this week, I interviewed Jonathan Carlson about his work and expectations of the conference. 

Jonathan Carlson

So you are researcher at Microsoft. How does that work? Are you part of the Bill & Melinda Gates Foundation?

A very common question indeed. We are part of Microsoft proper and have no affiliation with the Bill & Melinade Gates Foundation, though we do collaborate both with the foundation directly and with several academic groups that they fund. We are part of Microsoft Research, a division with some 850 researchers. Our specific group is the eScience group. We have computer scientists working on human genetics, astronomy, earth sciences, and infectious diseases. Our mission is to develop new technologies that use information science to advance basic science. The idea is that Microsoft will gain as technology becomes more useful and ubiquitous in our everyday lives.

Why is your work important?

The nice thing about working on HIV vaccine design is that the importance to human health is self-evident. What I particularly like, however, are the broader insights into the working of the human immune system and pathogens that we have gleaned from studying a virus that has so completely adapted to challenge our immune systems. As we hone in on HIV’s adaptive mechanisms, we gain insights into the workings of our immune system and how it interacts with viruses. A recent example of this is the work we did that confirmed the prevalent roll that mis-translation plays in the generation of T-cell epitopes. This potentially has broad implications for vaccine design.

Could you explain how HIV adapts to a patient?

We leverage the adage: If HIV is attacked, it adapts. This of course is probably true of all viruses, but HIV mutates at such an astonishing rate – 1:2 mutations per replication, with as many as 100 billion replications per day – that the adaptation occurs very nearly in real-time. In effect, each patient carries their own subspecies of virus that is uniquely adapted to that patient’s immuno-environment. This means that patients with common immune characteristics will likely harbor HIV strains with similar adaptations.

How do you study these adaptations?

To date, most of our work has focused on HLA proteins. These proteins mediate the adaptive immune response. An HLA protein’s role is to bind protein fragments inside the cell, then transport them to the cell surface. There, T-cells [immune cells] learn to recognize these fragments that are derived from foreign pathogens.

The interesting property of HLA proteins is that a given variant will only recognize a small set of potential peptides, while there are thousands of HLA alleles in the human population. Given the diversity of these proteins, and the specificity with which each variant recognizes peptides, the end result is that different immune systems target HIV (or any other pathogen) very differently.

That said, two patients who share an HLA variant will (with some probability) target some of the same HIV peptides. Thus we would expect patients who share an HLA allele to harbor HIV populations that share common adaptive mutations. Our work has focused on developing statistical evolutionary models that help us identify such patterns.So the idea is, if HIV is attacked it will adapt. Which means that studying adaptation can help us identifying what is attacking and how the attack is being evaded.

What are your expectations of the coming days?

I’ve never been to any conference like the Lindau Meetings (of course, there might not be anything else like it), so I’m not really sure what to expect of it. Pretty much every scientific meeting I’ve been able to attend has been centered around fairly specific scientific themes and has focused on the state-of-the-art science in the field. This meeting is completely different. It really has nothing to do with any specific science per se. Rather, it’s about meta-science: learning from both those who have successfully gone before you and “peers” who come from completely different scientific and cultural backgrounds. With the caliber of the participants, both laureates and young researchers, I have no doubt that I will learn a lot!

Thank you for the interview Jonathan and enjoy the conference!