Israeli Researchers Break New Ground in study linking herpes to brain damage

Stem cell technology used to turn the skin cells into brain cells was based in part on the discovery by this year's Nobel laureates in physiology or medicine.

By Dan Even | November 12, 2012 | Haaretz




Turning skin cells into brain cells, Israeli researchers are among those from several countries who broke new ground recently in understanding why certain people are more susceptible to an acute inflammation of the brain after being infected with a specific form of herpes.

The researchers found that the brain cells created from the skin cells of people with a particular mutation were unable to generate interferon, a protein typically released in response to the presence of pathogens, making them more likely to get infected after being exposed to the herpes virus. The study was published in the journal Nature last month.

"Interferon is an important mediator in the infection processes in the body, and is used in medicine to treat certain types of hepatitis - and we have found that its absence is what leads to an increased risk of damage to brain cells," said Itai Pessach, a pediatrician at the Edmond and Lily Safra Children's Hospital at Sheba Medical Center, Tel Hashomer, and one of the lead researchers.

The researchers, including Fabien Lafaille from the Sloan-Kettering Institute and Shen-Ying Zhang from Rockefeller University, both in New York, were focusing on children with a genetic variant that makes them prone to encephalitis, an acute inflammation of the brain, resulting from being infected by herpes simplex virus 1.

After transforming the skin cells of carriers into stem cells, the researchers turned the stem cells into neurons under conditions simulating a brain cell environment, to see how the lab-generated brain cells would react when infected with HSV-1.

"We were looking to examine processes in brain cells," said Pessach, adding that since scientists can't watch the cells in a living brain, being able to create them from other cells using stem cell technology is a "significant advantage."

The herpes element of the Nature study was based on research conducted in 2007 by Jean-Laurent Casanova of Rockefeller University, who identified the TLR3 genetic mutation, carriers of which are prone to developing herpes-induced encephalitis. Until now, researchers have not known what exactly makes TLR3 carriers more likely to develop the infection.

Life-threatening virus

HSV-1 is the primary cause of herpes infections on the mouth and lips, including cold sores, and is transmitted by drinking from shared cups or bottles and by kissing. Though HSV-2 is the main cause of genital herpes, HSV-1 can also cause it.

Most herpes infections do not cause serious complications, but the virus can be life-threatening in babies or people with weakened immune systems.

Other researchers include Yechiel Elkabetz from Tel Aviv University's Sackler School of Medicine and researchers from France and Saudi Arabia.

The stem cell technology used to turn the skin cells into brain cells was based in part on the discovery by this year's Nobel laureates in physiology or medicine, John B. Gurdon and Shinya Yamanaka, that "mature cells can be reprogrammed to become pluripotent," meaning that they are capable of differentiating into one of many cell types. This has helped lay the groundwork for regenerative medicine, the idea of repairing the body by regenerating damaged cells, tissues or organs.

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