Study Describes Structure of Tumor Herpes Virus Associated With Kaposi's Sarcoma

Key Points

  • Researchers used a new electron-counting technology called cryo–electron microscopy.
  • The virus is composed of approximately 3,000 proteins, each consisting of roughly 1,000 amino acids.
  • It contains 46 unique conformers of the major capsid protein, the smallest capsid protein, and the triplex proteins Tri1 and Tri2.

Researchers from the University of California, Los Angeles (UCLA) have provided the first description of the structure of the herpes virus associated with Kaposi’s sarcoma. The findings, published by Dai et al in Nature, answer important questions about how the virus spreads and provide a potential roadmap for the development of antiviral drugs to combat both that virus and the more common Epstein-Barr virus, which is present in more than 90% of the adult population and is believed to have a nearly identical structure.

In the study, the UCLA team showed in the laboratory that an inhibitor could be developed to break down the herpes virus. Kaposi’s sarcoma–associated herpes virus, or KSHV, is one of two viruses known to cause cancer in humans.

KSHV and Epstein-Barr

KSHV was discovered in the mid-1990s at the height of the AIDS epidemic, when as many as half of people with AIDS were found to have the virus; it continues to be the most common cancer-causing virus associated with AIDS. In low-income countries, KSHV also poses a significant risk to patients not diagnosed with AIDS. In sub-Saharan Africa, for example, approximately 40% carry the virus, and Kaposi’s sarcoma is among the most common cancers in the region.

No vaccine or drug has been developed to prevent or treat KSHV or the cancer it causes; nor has a vaccine or treatment been developed for Epstein-Barr, another member of the herpes virus family and one of the most common viruses in humans. Epstein-Barr is best known for causing infectious mononucleosis, but it is also associated with an increased risk for several cancers, such as nasopharyngeal carcinoma.

Knowing the atomic structure of the protein shell, or capsid, of the herpes virus could be an important step toward antiviral therapies. It would give scientists specific targets in the protein shell that are critical to the ability of the virus to spread.

Without that atomic description, “it was impossible to target specific sites of the enormous capsid to disrupt the spread of the virus,” said Z. Hong Zhou, PhD, Professor of Microbiology, Immunology, and Molecular Genetics, a member of UCLA's California NanoSystems Institute, and a senior author of the research. “Our study provides that atomic description.”

Major Findings

Researchers used a new electron-counting technology called cryo–electron microscopy, whose inventors won the 2017 Nobel Prize in chemistry. The technology enabled the scientists to see the herpes virus with unprecedented resolution, which in turn allowed them to create a three-dimensional atomic model of the virus. The virus is composed of approximately 3,000 proteins, each consisting of roughly 1,000 amino acids. It contains 46 unique conformers of the major capsid protein, the smallest capsid protein, and the triplex proteins Tri1 and Tri2.

“The high pressure caused by the densely packed herpes virus genome also means that if one unit is weakened, the whole structure will fall apart,” said Ren Sun, PhD, Professor of Molecular and Medical Pharmacology and Bioengineering, a member of the California NanoSystems Institute, and the study’s co–senior author. “This offers a distinct advantage as a mechanism for drug development.”

Dr. Sun’s group is following up on these findings by screening for drugs that could perform similar antiviral actions in humans.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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