Science, Space and Technology News 2024
University of Chicago researchers have discovered how HIV’s capsid structure enables the virus to enter a cell’s nucleus, providing new insights into the virus’s replication mechanism and potential targets for drug development. This study emphasizes the importance of the capsid’s elasticity and the nuclear pore’s role, marking a significant advancement in the understanding of HIV and offering new strategies for combating the virus.
The finding, created by a simulation of thousands of proteins interacting, will point the way to a better understanding of HIV as well as suggest new targets for therapeutic drugs. “For example, you could try to make the HIV capsid less elastic, which our data suggests would hamper its ability to get inside the nucleus,” said Arpa Hudait, a research scientist at UChicago and first author of the paper.
The capsid is a complex piece of machinery, made of more than a thousand proteins assembled into a cone-like shape, with a smaller and larger end. To get into the host cell’s nucleus, it must sneak in. But scientists didn’t know exactly how this happens. “This part has been a mystery for years,” said Voth, the senior author on the paper. “For a long time, no one was sure whether the capsid broke apart before entering the pore or afterward, for example.
To fill in the gaps, Hudait built a painstaking computer simulation of both the HIV capsid and the nuclear pore complex—accounting for thousands of proteins working together. The finding may help explain why capsids are cone-shaped, rather than a shape like a cylinder, which might seem at first easier to slip through a pore.
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