The Epstein–Barr Virus Wears Chain Mail

The Epstein–Barr virus and its relatives in the herpesvirus family are known for their longevity. They persist in host tissues for years, causing diseases like mononucleosis, Kaposi’s sarcoma and herpes, and are notoriously difficult to kill. University of California, Los Angeles, biophysicist Z. Hong Zhou thinks the secret to herpesviruses’ resilience may be a layer of microscopic chain mail.

Zhou and his colleagues examined the outer shells, or capsids, of a primate herpesvirus under an electron microscope and saw a pattern of interlocking protein rings. Those rings form a mesh that can withstand intense pressures and explain why herpesviruses can maintain decades-long infections.

The study, published in the October 7 issue of Structure, marks the first time anyone has been able to bring the herpesvirus structure into focus—literally. Solving the configuration of a viral capsid requires both the ability to discern individual molecules and the ability to see how those molecules fit together in the viral shell.

Herpesviruses are so big that they don’t fit within most electron microscopes’ fields of view. Trying to understand their structure by looking at atomic-resolution images is like trying to understand the anatomy of an elephant based on extreme close-ups—easier said than done. Once Zhou’s team brought the image into focus, however, they saw a familiar pattern. The interlocking mesh pattern is very similar to the structure other virologists have found in bacteriophages, a family of viruses that infect bacteria, which suggests that herpesviruses and bacteriophages may share a common evolutionary origin. “We never would have seen that connection based on genetic sequences alone,” says Jack Johnson, a virologist at The Scripps Research Institute not involved with the study who first discovered the chain mail pattern in bacteriophages. “This study shows how important it is to actually look at the structure.”

These results may also open up new possibilities for vaccine development. According to Zhou, understanding the geometry of chemical bonds within the chain mail may help researchers develop antiviral particles that can break them apart. “Most viruses do not have these rings,” Zhou says. “Instead, their capsids are made of ‘bricks’ that disassemble once they’ve entered a host cell.” These capsid bricks are like LEGO blocks ; even though they fit together tightly, they’re meant to be pulled apart. Herpesviruses, however, are built to last.

They have to be. Their DNA is packed into the capsid so tightly that the pressure it exerts on the capsid wall is about 50 times greater than the pressure Earth’s atmosphere exerts at sea level. Techniques that neutralize viruses which have LEGO-style capsids often don’t work on Epstein–Barr, herpes or Kaposi’s sarcoma viruses, much to the disappointment of many vaccine developers.

Solving the structure is only a first step toward a vaccine, but a crucial one. Although no one has developed a vaccine against bacteriophages (“There really isn’t a market for immunizing bacteria,” Johnson says), now that human pathogens like Epstein–Barr and herpes simplex have been added to the viral chain mail club, that’s likely to change.

Read more at www.scientificamerican.com