The human intestinal tract, or gut, is best known for its role in digestion. But this collection of organs also plays a prominent role in the immune system. In fact, it is one of the first parts of the body that is attacked in the early stages of an HIV infection. Knowing how the virus infects cells and accumulates in this area is critical to developing new therapies for the over 33 million people worldwide living with HIV. Researchers at the California Institute of Technology (Caltech) are the first to have utilized high-resolution electron microscopy to look at HIV infection within the actual tissue of an infected organism, providing perhaps the most detailed characterization yet of HIV infection in the gut.
The team's findings are described in the January 30 issue of PLOS Pathogens.
"Looking at a real infection within real tissue is a big advance," says Mark Ladinsky, an electron microscope scientist at Caltech and lead author of the paper. "With something like HIV, it's usually very difficult and dangerous to do because the virus is an infectious agent. We used an animal model implanted with human tissue so we can study the actual virus under, essentially, its normal circumstances."
Ladinsky worked with Pamela Bjorkman, Max Delbrck Professor of Biology at Caltech, to take three-dimensional images of normal cells along with HIV-infected tissues from the gut of a mouse model engineered to have a human immune system. The team used a technique called electron tomography, in which a tissue sample is embedded in plastic and placed under a high-powered microscope. Then the sample is tilted incrementally through a course of 120 degrees, and pictures are taken of it at one-degree intervals. All of the images are then very carefully aligned with one another and, through a process called back projection, turned into a 3-D reconstruction that allows different places within the volume to be viewed one pixel at a time.
|Contact: Deborah Williams-Hedges|
California Institute of Technology