Electron microscopy helps define HIV’s spikes

On each particle of HIV, there are scattered several spikes — composed of glycoprotein — that initiate the infection of healthy cells. The glycoprotein is a candidate target for potential vaccines against the virus; however, little is known about the structure and distribution of the spikes.

Now Ping Zhu and his colleagues at Florida State University in Tallahassee and at the National Cancer Institute at Frederick and the National Institutes of Health in Bethesda, both in Maryland, have further defined the spikes using
cryoelectron microscopy.

With an electron microscope from FEI Co. in Eindhoven, the Netherlands, and a slow-scan CCD camera made by Tietz Video and Image Processing Systems GmbH in Gauting, Germany, the researchers acquired single-axis-tilt tomographic images of unfixed simian and human immunodeficiency viruses. Using a magnification of 43,200x and an underfocus of 4 to 6 μm, they determined that each HIV particle carries approximately 14 unevenly distributed spikes and each simian virus particle, about 73 spikes. The spikes of the human virions exhibit some clustering.

With the same setup, they acquired a three-dimensional image of the 13.7-nm-tall trimeric spikes, with a 10.5-nm-diameter trimer head that sits atop three individual legs, each about 1.9 nm high. Each of the three subunits within the trimer head is composed of three separate lobes. The model of the spike was derived by averaging more than 6000 individual spike images.

The scientists suggest that more spikes per particle correlates with increased infectivity and that clustering may have a role in fusion efficiency. Clustering, they believe, ultimately might lead to antibody-mediated neutralization of the virus. They report their findings in the May 24 online edition of Nature.