Scientists have created the best image yet of the cocoon-like container that carries HIV’s genome. Resembling a long, intricately woven basket, the inner shell, or capsid, of HIV shown in this video might be a new target for future antiretroviral therapies.
Normally, when HIV infects a cell, the capsid is injected into the host cell’s fluid interior, where it releases two copies of single-stranded RNA and associated enzymes. More than half of current antiviral drugs for HIV target the next stage of the process, when the viral RNA is converted to DNA for entry into the host cell’s nucleus. If new drugs can attack the HIV capsid, the virus could be stopped much earlier, before ever entering the cell.
The capsid has an elongated fullerene-type structure. Fullerenes, named after the architect Buckminster Fuller, are carbon-based molecules patterned with repeating polygonal shapes similar to a soccer ball. Most of the capsid protein, p24, is arranged into six-sided units, or hexamers. The capsid’s cone-like shape comes from 12 five-sided p24 units, or pentamers, that form the most tightly rounded corners of the capsid shell and allow it to become a closed container. Linking the pentamer and hexamer units are double- and triple-sided units of p24 (dimers and trimers, respectively) that help hold the structure together.
Capsids have been difficult to study because individual imaging techniques had not produced high enough detail. By combining several methods, including cryo-electron microscopy and cryo-electron tomography, scientists funded by the National Institutes of Health pieced together the individual polygonal units of the capsid like a jigsaw puzzle to determine its structure in detail.
The team then sent all of the molecular data on the capsid to an NIH-funded technology resource center, where scientists used a supercomputer to create an atomic-resolution picture of the capsid. All 4.2 million atoms making up the approximately 1,300 p24 copies of the structure appear in the video.
Now that scientists know how HIV’s inner vessel looks, they are searching it for cracks. Potential drugs that would target the capsid could more efficiently keep the virus at bay than current treatments.
The research reported in this article was funded in part by the National Institutes of Health under grants P41GM104601, P50GM082251 and R01GM085043.
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