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Small Genes May Help “Mono” Virus Hide in Humans

By Edward R. Winstead

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Infectious Diseases

The Epstein-Barr virus.
Five small genes discovered in the virus that causes mononucleosis may explain the virus’s remarkable ability to hide in the human body for decades without being detected by the immune system.

The five genes make molecules that can reduce the activity of other genes, such as human genes in cells infected by the virus.

For instance, the virus may enter a human immune cell and produce a molecule that suppresses a human gene that would normally help detect the virus. As a result, the human immune system does not recognize the virus.

The molecules are known as microRNAs.

“It’s always been a mystery how large DNA viruses manage to stay inactive in the body for years without being recognized and cleared by the immune system,” says Thomas Tuschl of The Rockefeller University in New York, who led the team that discovered the genes. “MicroRNAs may explain that mystery.”

The viral genes have just been identified, and at this point there is no experimental evidence that the viral genes suppress the human immune system. But the circumstantial evidence, reported in today’s issue of Science, is intriguing.

The circumstantial evidence comes from comparisons, done on the computer, of microRNAs and human genes. The computer showed that some of the microRNAs are similar to genes in human immune cells. This suggested to the researchers that the microRNAs may target these genes.

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Further research revealed that the “targeted” human genes are active in cells that the virus tends to infect, so-called B cells, which are part of the human immune system.

All this, says Tuschl, is unlikely to be a coincidence. The virus, he suspects, evolved the small genes as a way to disable enemy immune cells. Indeed, the virus could have produced the small genes without too much evolutionary effort.

“The key message of this study is that virologists have to look at the virus again more carefully,” says Tuschl. “Here are five genes that have been overlooked, and these could be the key to understanding how this virus eludes the immune system for so long.”

One of the most common human pathogens, the mononucleosis virus, also called the Epstein-Barr virus, is a type of herpes virus. Most people around the world are infected at some point during their lives. Children in developing countries typically become infected with the virus, and these infections usually cause no symptoms or a mild, brief illness.

Infections during childhood are less common in developed countries. When a person is infected during adolescence or young adulthood, the result is infectious mononucleosis between 35 and 50 percent of the time. The symptoms include fever, sore throat, and swollen glands.

In the last three years, microRNAs have been identified in plants and animals; the human genome has at least two hundred. The findings published today will give scientists new reasons to hunt for these small but influential molecules in other viruses.

Pfeffer, S. et al. Identification of Virus-Encoded MicroRNAs. Science 304, 734-736 (April 30, 2004).

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