Using a new technique known as cryo-electron tomography, scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), along with colleagues from the Johns Hopkins University and the Max Planck Institute, have succeeded in imaging the three-dimensional structure of the Herpes Simplex virus 1 (HSV1). The term "cryo" means that the specimens were preserved and observed in a thin film of ice, thus maintaining their native structures. This is the first study using this technique to obtain three-dimensional images of a complete virus whose structure can vary from particle to particle.

Smaller and simpler viruses whose structures show a high degree of symmetry have been studied by cryo-electron microscopy, exploiting that symmetry. HSV1 presents a special challenge for imaging at the molecular level, since most of its structure does not conform to that symmetry. Tomography, however, which involves tilting the specimen (just as in the clinical imaging technique of computerized axial tomography, known as CAT scans, but on a much smaller scale), proved capable of imaging the complete virus.

The study showed that it is possible to obtain three-dimensional images of asymmetric viruses, which should lead to a greater understanding of how these viruses infect cells of the human body. Cryo-electron tomography will make it possible to study the interaction of the virus with antibodies and to determine how the virus is inactivated by some antibodies but not others. This will, according to the researchers, yield clinically important information as studies using this technique continue. Beyond viruses, there are many large cellular components which are asymmetric and which have not been amenable to study before. These can now be productively imaged with cryo-electron tomography.

HSV1 is a human pathogen that causes oral cold sores and a rare, but severe, form of encephalitis, an inflammation of the brain. The herpes virus family includes other pathogens that cause genital herpes, chicken pox and shingles. These viruses can remain dormant for years after an initial infection, reactivating when the immune system is under stress.

The study was published in the journal Science on November 21, 2003. The NIAMS is part of the U.S. Department of Health and Human Services' National Institutes of Health, the leading Federal agency in biomedical and behavioral research.

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Grünewald K, Desai P, Winkler DC, Heymann JB, Belnap DM, Baumeister W, Steven AC. Three-dimensional structure of herpes simplex virus from cryo-electron tomography. Science 2003;302:1396-1398.

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