Viral Armor

BY PLUCKING CYPOVIRUS'S tiny crystalline home from the insect cells that the pathogen infects, researchers have solved the first atomic-level X-ray structure of a virus's protective crystalline casing (Nature 2007, 446, 97).

The four-year research endeavor is a "stunning proof of principle," comments David Stuart, a structural biologist at the Wellcome Trust Centre for Human Genetics, in Oxford, England. This effort has produced the first atomic-level structure of any natural intracellular crystal. Moreover, the protein crystals in this study are the tiniest to ever have been solved, he says. Important biological molecules such as membrane proteins often yield only small crystals, so the techniques used to study cypovirus's minute home will have broad application.

Cypovirus lodges itself in a crystalline casing to protect its enzymes and RNA-based genome. Fasséli Coulibaly and Peter Metcalf at the University of Auckland, in New Zealand, and colleagues in Japan and Switzerland found that polyhedrin, the protein that forms cypovirus's crystalline habitat, is composed of a β-sheet core flanked by four α-helices. Polyhedrin self-assembles, primarily through hydrophobic interactions, into a trimer. A quartet of these trimers organize into a tetramer, and two tetramers form the repeating unit of the crystal.

The cypovirus particles embedded within the polyhedrin crystal give the casing the mottled appearance of Gruyère cheese but do not disrupt the crystal's exquisite symmetry, writes Felix A. Rey of the Pasteur Institute, Paris, in an associated commentary.

These protein casings are "pretty amazing," Metcalf says. "Normally, structural biologists have to grow crystals in pure solution, yet this protein crystallizes in a cellular soup around the virus particle." The protein-protein contacts within the crystal casing are stronger than many antibody-antigen interactions, he adds.

In fact, these 1-2-μm crystal habitats are impervious to strong acids and high temperatures. These characteristics help protect the embedded virus particles for up to several years. The only thing that dissolves these crystals is strong base, such as the pH 10 environment of insect larvae guts, where the virus initiates infection.

The new X-ray structure provides a blueprint for building a sturdy microscale box, revealing structural insights that researchers hope to extend into the nanoscale. Metcalf says nucleotides can be trapped in the casings for three years, a feat suggesting that the crystals might be chemically modified to carry drugs or probes.

"Here, evolution has done a big part of the design to produce a fantastically tough crystal lattice that is designed to specifically incorporate larger objects, protect them for years from harsh environmental insults, and then release them on a chemical signal," Stuart says. "If we can't think of useful adaptations for that type of system, then we are not being very innovative."