The tactics that HIV uses to infect cells have been visualised in greater detail than ever before, thanks to a microscopy technique that allows even structures within viruses to be seen.
Conventional light microscopes cannot resolve structures that are smaller than about 200 nanometres because they are limited by the wavelength of visible light. Viruses, which typically measure 25 to 300 nm, are just too small to see.
One way around this has been to tag proteins with fluorescent markers, activate them one at a time, and then map the locations of all these markers into a composite image. Markers can interfere with protein function, though, making it difficult to study proteins in action.
Nathalie Arhel at the Pasteur Institute in Paris and her colleagues have modified this technique and inserted a six-amino-acid motif into the enzyme that HIV uses to integrate its DNA into its host’s genome. The motif is too short to affect the enzyme’s function, but long enough to bind to a fluorescent marker molecule.
They used the technique to take a closer look at HIV. Previously, it was unclear whether the virus’s genetic material is released into the cytoplasm of the host cell, or whether it remains in a container called a capsid until reaching the cell’s nucleus. The technique has revealed that it remains in the capsid – information that may provide opportunities for targeting the virus before it integrates its DNA.
Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1013267109).
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