As a retrovirus matures, the two parts of its shell protein (red and blue or yellow and blue) dramatically rearrange themselves, twisting and moving away from each other. Credit: EMBL/T.Bharat

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have for the first time uncovered the detailed structure of the shell that surrounds the genetic material of retroviruses, such as HIV, at a crucial and potentially vulnerable stage in their life cycle: when they are still being formed. The study, published online today in Nature, provides information on a part of the virus that may be a potential future drug target.

Retroviruses essentially consist of genetic material encased in a protein shell, which is in turn surrounded by a membrane. After entering a target cell in the case of HIV, one of the cells in our immune system the virus replicates, producing more copies of itself, each of which has to be assembled from a medley of viral and cellular components into an immature virus. "All the necessary components are brought together within the host cell to form the immature virus, which then has to mature into a particle that's able to infect other cells" says John Briggs, who led the research at EMBL. "We found that when it does, the changes to the virus' shell are more dramatic than expected."

Enlarge

The role and shape of the protein shell (blue/orange) changes from the immature (top) to the mature form of the virus (bottom). Credit: EMBL/T.Bharat

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As a retrovirus matures, the two parts of its shell protein (red and blue or yellow and blue) dramatically rearrange themselves, twisting and moving away from each other. Credit: EMBL/T.Bharat

Although the virus shells imaged in this study were derived from the Mason-Pfizer monkey virus and made artificially in the laboratory, they closely resemble those of both this virus and HIV which are very similar in their natural forms.

"We still need a lot more detailed information before drug design can really be contemplated," Briggs concludes, "but finally being able to compare mature and immature structures is a step forwards."

Journal reference: Nature

Link:
Shape-shifting shell: Structure of a retrovirus at a potentially vulnerable stage