Deep-Sequencing Technique Holds Promise of Finding Viral Links to MS, Similar Diseases

(SALT LAKE CITY)—A team led by University of Utah infectious diseases researchers has found the hepatitis G virus in the brain of a deceased woman with multiple sclerosis (MS).

The discovery is the first time that hepatitis G, or GBV-C, has been found in a human brain and it shows the value of “deep-sequencing” technology in searching for viral causes of MS-like illnesses, according to infectious diseases expert John D. Kriesel, M.D., associate professor of internal medicine at the University of Utah School of Medicine and first author of the new study.
“We believe deep sequencing is an important new technology that may allow us to find viruses that trigger MS or MS-like diseases,” Kriesel says. “However, our study does not definitively link the GBV-C virus to MS.”

Kriesel and colleagues at the U of U, ARUP Laboratories, and the Human Brain and Spinal Fluid Research Center, Los Angeles, published their findings in PLoS One in early March.

MS attacks the sheaths surrounding nerves in the central nervous system (CNS), interfering with the transmission of nerve signals between the brain, spinal cord, and other parts of the body. An estimated 400,000 Americans have the disease, with symptoms that range from fatigue, numbness, and cognitive problems to speech disorders, seizures, and difficulty breathing. Some people with progressive MS eventually lose the ability to speak, walk, and feed themselves. Viruses long have been suspected as a trigger for the development of MS.
To look for potential viral causes of MS, the researchers extracted RNA from brain taken from 17 people who died with MS compared with brain RNA from 11 others who died from other causes. This technique, called “deep sequencing”, allowed the researchers to detect 4 million to 10 million short sequences of RNA from each brain. “Most studies of potential viral causes of MS have focused on DNA viruses,” Kriesel says. “But DNA viruses can be latent (quiescent) in the central nervous system, making it hard to know whether they actually caused a disease.  But RNA reflects active genes, so we focused on detecting possible viral RNA”
However, RNA is unstable and short-lived, so, after extracting the RNA sequences, the researchers used a process called reverse transcription to change the RNA into complementary DNA (cDNA). Then they compared the tens of millions of newly made cDNA sequences with a National Library of Medicine database containing more than 600,000 viral DNA sequences, something Kriesel compares to “throwing the kitchen sink at the wall.” But it worked, at least in one subject, and they identified GBV-C in the brain of one deceased person who suffered from MS.
Although its name suggests otherwise, the hepatitis G virus is not associated with acute or chronic hepatitis. It can cause liver inflammation but there is little proof that causes serious liver damage and it has never been isolated from brain before.

As sequencing and analysis techniques get better and better, the researchers hope to identify more viruses in the brains of persons who had MS, particularly the primary progressive form of this disease.  In the future, the group plans to use sequences taken from existing brain biopsies—occasionally done to exclude cancer—to look for viruses in people with MS and other demyelinating diseases.

“We would like to bring this work into the realm of the living by applying our deep sequencing technique to persons with acute MS or other MS-like diseases,” Kriesel says. “In this manner, we hope to catch a virus or other microbe in the act of triggering MS.”

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