AIDS at 25

After my initial post in which I raised the question of whether science still has a significant place in the conference, I began to sniff it out. In the afternoon, I attended a session called "Novel Targets for Drug Development." As the name suggests, the symposium was designed to review some new targets for anti-HIV drugs. The audience was the largest I've ever seen for a scientific talk--easily 600 people were in attendance. Nearly every seat in the enormous conference room was taken, but I found it difficult to gauge who it was composed of--other scientists, media, activists, people living with HIV/AIDS?

When the scientists began their PowerPoint presentations, they didn't appear to be in doubt of the audience: other scientists. Their slides were complete with the lengthy acronyms, complex diagrams and figures, and experimental detail typical of scientific talks. Aside from feeling a little bit like I was back in grad school, I was thankful that my training included copious amounts of immunology and cell biology.

First up, and the most interesting of the bunch to me, was Dr. Warner C. Greene from UC, San Francisco. Dr. Greene studies a fascinating protein complex called APOBEC3, and its best-known member, APOBEC3G, which is part of a cell's innate defense system against retroviruses (viruses such as HIV that possess and RNA genome and rely on the enzyme reverse transcriptase to replicate). The acronym APOBEC3 stands for--watch out--apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3.

Dr. Greene presented some of his work, published in Nature in 2005, showing that the protein APOBEC3G leads a sort of double life. In resting CD4 T cells, the white blood cells that are the main target of HIV, it protects the cell against infection. But in activated CD4 T cells (cells that have been primed for an immune response), HIV is able to circumvent or disable APOBEC3G's anti-viral property, so the cell is no longer protected. Furthermore, he showed that if you artificially disable the form of APOBEC3G that naturally exists in resting cells, the cells became susceptible to infection. His insights are that resting T cells actively repel HIV, and that this ability hinges on APOBEC3G.

Greene also presented more recent work characterizing the two forms of APOBEC3G that exist in resting and activated T cells. By better understanding the mechanism by which APOBEC3G protects cells and the mechanism by which HIV dismantles its protective shield, Greene hopes to be able to develop new anti-HIV therapies. For instance, he may be able to figure out a way to get cells to convert the protein back from its permissive form to its protective form.

This research is still in its infancy, but it provides a fascinating glimpse of the inner workings of the cells that are the gateway to HIV infection. Keep an eye on the science of APOBEC3G... With a name like that, who could forget it?