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

Jun 04, 2012
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 encased in a protein , which is in turn surrounded by a membrane. After entering a – in the case of , one of the cells in our immune system – the 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."

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

Both the mature and immature virus shells are honeycomb-like lattices of hexagon-shaped units. Using a combination of electron microscopy and computer-based methods, Briggs and colleagues investigated which parts of the key proteins stick together to build the honeycomb of the immature shell. These turned out to be very different from the parts that build the mature shell. This knowledge will help scientists to unravel how the immature virus is assembled in the cell and how the shell proteins rearrange themselves to go from one form to the other.

This video is not supported by your browser at this time.
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

Findings such as these may one day prove valuable to those wanting to design new types of anti-retroviral therapies. Many anti-retroviral drugs already block the enzyme that would normally separate components of the immature shell to allow it to mature. But there are currently no approved drugs that act on that shell itself and prevent the enzyme from locking on.

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."

Explore further: Brand new technology detects probiotic organisms in food

add to favorites email to friend print save as pdf

Related Stories

New electron microscopy images reveal the assembly of HIV

Jun 23, 2009

Scientists at the European Molecular Biology Laboratory (EMBL) and the University Clinic Heidelberg, Germany, have produced a three-dimensional reconstruction of HIV (Human Immunodeficiency Virus), which shows ...

Scientists reveal complete structure of HIV's outer shell

Jan 19, 2011

A team of scientists at The Scripps Research Institute and the University of Virginia has determined the structure of the protein package that delivers the genetic material of the human immunodeficiency virus (HIV) to human ...

New HIV vaccine approach targets desirable immune cells

Sep 01, 2011

Researchers at Duke University Medical Center, Beth Israel Deaconess Medical Center and Harvard Medical School have demonstrated an approach to HIV vaccine design that uses an altered form of HIV's outer coating or envelope ...

How TRIM5 fights HIV

Apr 20, 2011

Thanks to a certain protein, rhesus monkeys are resistant to HIV. Known as TRIM5, the protein prevents the HI virus from multiplying once it has entered the cell. Researchers from the universities of Geneva and Zurich have ...

Recommended for you

Atomic structure of key muscle component revealed

23 minutes ago

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0