Chasing a common cold virus

Oct 22, 2012 by Susheela Bhat
Chasing a common cold virus
A rendering of the human adenovirus, showing the outer capsid proteins (shown in multiple colors).

(—As the cold and flu season makes its annual visit, a team of researchers, using Argonne's Advanced Photon Source, continue to complete a detailed map of the human adenovirus—one of several viruses responsible for the common cold.

Although human adenovirus is usually not deadly, it is a seasonal nuisance to some and can cause in others.

In the early 1990s, Glen Nemerow, professor and principal investigator at the Immunology and Microbial Science division of The Scripps Institute, switched from his previous research on Epstein-Barr to human adenovirus. "It is easy to grow and manipulate, which made (and makes) it an excellent model for studying host-," said Nemerow.

Although the had been studied since the early 1950s, most research tended to focus on subunits of the virus, such as major proteins, because the intact virus is dauntingly large. Nemerow decided instead to examine the entire molecular structure of human adenovirus. He wanted to see how proteins self-assemble to form the complete virus.  A major goal of the research is to try to improve how the virus could be used for —and potentially, . Nemerow teamed up with Vijay Reddy, an associate professor at Scripps, to investigate the 3-D shape of human adenovirus using a technique called .

First the researchers needed to grow a crystal of the virus. This presented several challenges. For one, a complete human adenovirus sports fiber "spikes" that help it attach to a , but also prevented researchers from successfully growing a crystal. One of the first steps the scientists took was to engineer a human adenovirus molecule without the fiber spikes. Altogether, getting usable crystals took five years.

When they were ready to test the virus crystal, Nemerow and Reddy partnered with Argonne biophysicist Robert Fischetti and started their work at the 's General Medicine and Cancer Institute's Collaborative Access Team (GM/CA) beamline.

Unlike other beamlines they'd tested, the GM/CA beamlines produce intense X-ray beams that allowed the researchers to collect high-quality data from the virus crystals. This gave researchers a detailed 3-D image of the structure—the largest structure of any biomolecule determined by X-ray crystallography to date.

"Without the beamline, we would have been stymied on this project," said Nemerow. The APS beamline, they hoped, would reveal where electrons were clustered in the human adenovirus molecule and how they were connected.

Over the course of the project, Fischetti and colleagues modified the beamline to improve the uniformity of the beam. They installed smoother mirrors, reduced the amount of radiation damage to the crystals, and provided the team more flexibility to focus the beam. This helped Nemerow and Reddy hone the first map of the human adenovirus' structure, which they published in the journal Science.

Nemerow and Reddy compared their map to what was already known about the human adenovirus from previous research. "We weren't able to assign an identity for all 12 of the proteins in human adenovirus to the electron density we mapped out," Nemerow said. "There were also four major 'cement' proteins we could not identify or assign—either because they haven't been seen yet, were too disordered or because we didn't have enough data at the time."

Cement proteins, as their name suggests, bind major proteins to the virus shell, or capsid.

Nemerow and Reddy found major capsid proteins tended to be easier to see in an electron density map because of their symmetry and general stability, but cement proteins proved the sticking point. "We don't know the structures of cement proteins at high resolution yet, because they are difficult to purify by themselves—which makes them even harder to crystallize," Reddy explained. "The cement proteins bind to major capsid proteins, like cement to bricks, and mediate interactions between them." Because cement proteins are flexible and dynamic, they can degrade easily from radiation damage or fail to produce diffraction under a high-resolution X-ray.

Fischetti and colleagues are upgrading the GM-CA beamlines to provide smaller and more intense X-ray beams to help scientists create clearer images from their crystals. Once the upgrade is completed, Nemerow and Reddy can continue to complete their map of the human adenovirus, so that one day a seasonal nuisance may become a powerful tool for human health.

Explore further: Celebrating 100 years of crystallography

Related Stories

Scientists isolate portion of virus that causes pink eye

Apr 15, 2010

Viral keratoconjunctivitis, also known as pink eye, is a common, uncomfortable and highly contagious condition. There is no known effective treatment for this adenovirus infection that can force some individuals into isolation ...

Research could lead to more comprehensive flu vaccines

Mar 27, 2009

( -- New findings from research performed on the influenza virus using X-rays generated by the Advanced Photon Source (APS) at the U.S. Department of Energy's Argonne National Laboratory may help ...

Recommended for you

The fluorescent fingerprint of plastics

11 hours ago

LMU researchers have developed a new process which will greatly simplify the process of sorting plastics in recycling plants. The method enables automated identification of polymers, facilitating rapid separation ...

Water and sunlight the formula for sustainable fuel

15 hours ago

An Australian National University (ANU) team has successfully replicated one of the crucial steps in photosynthesis, opening the way for biological systems powered by sunlight which could manufacture hydrogen ...

Rice chemist wins 'Nobel Prize of Cyprus'

15 hours ago

Rice University organic chemist K.C. Nicolaou has earned three prestigious international honors, including the Nemitsas Prize, the highest honor a Cypriot scientist can receive and one of the most prestigious ...

Researchers create engineered energy absorbing material

16 hours ago

( —Materials like solid gels and porous foams are used for padding and cushioning, but each has its own advantages and limitations. Gels are effective as padding but are relatively heavy; gel performance ...

User comments : 0