Remember when we learned in class about capsid morphology? We learned that viruses have 3 different types of morphology - icosahedral, helical, and complex - and that HIV falls within the complex category. I was excited to find today that some new research on HIV, published this month in the journal Cell and conducted by researchers at The Scripps Research Institute, builds very nicely on what we already know about the structure of the HIV capsid.
As we learned in class, the protein capsid surrounds the genetic material of the virus. We also saw pictures of several capsids in class, including (I'm pretty sure) one of the HIV capsid. Previously, scientists knew that the HIV capsid was an arrangement of about 250 hexagonal protein building blocks, called the CA. Sets of 6 CA protein molecules make up hexamers, and the ends of shell are completed with 7 and 5 protein pentamers (remember trying to spot the pentamers?). In the past, the group of scientists who conducted this study visualized these hexamers using electron microscopy, and then x-ray crystallography. However, this study is the first to describe the high-resolution molecular structure of the CA. Growing 3D crystals of the CA hexamer had been extremely difficult, but for this study scientists engineered CA proteins that would provide sturdy links between crystals. As a result, they were able to visualize the CA hexamer at a resolution of 2 Angstroms - an unprecedented level of detail. At this resolution, scientists were able to see the precise location of the side chains on the alpha helices that are responsible for stabilizing the structures. They were also able to see "flexibility" in the structure, as well as connections between the C-terminal ends and N-terminal ends of adjacent CA protein molecules.
This kind of detailed understanding of the HIV capsid structure provides new opportunities for interventions that could break apart or destabilize the capsid. For example, interventions could inhibit assembly of the capsid or facilitate its degeneration. The article mentioned, for example, designing small molecules that could be inserted at strategic positions to destabilize the capsid.
I was excited to read about a study that directly applies something we have learned about - viral structure, and specifically capsid morphology - to the real-life problem of HIV. I think this article illustrates beautifully how basic biological principles and understanding, which can often feel far removed from real life, can have huge implications for public health in the future. Whether or not this structure actually leads to the development of an effective intervention remains to be seen, but it seems to me that the greater our understanding of viruses, especially at the atomic level, the greater the chance that we will be able to intervene effectively.
The article can be found at: http://www.sciencedaily.com/releases/2009/06/090612163537.htm.