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July 10, 2001
Scientists Record Movement of Herpes simplex Virus in Nerve Cell

A team of scientists working at the Marine Biological Laboratory are the first to observe and record the movement of the Herpes simplex virus within a living nerve cell

Woods Hole, MA, and Providence, RI — For the first time, scientists have observed the movement of the Herpes simplex virus from a nerve ending to a cell body within a living nerve cell. A team of researchers led by Elaine Bearer, M.D., Ph.D., of Brown University conducted much of the work last summer at the Marine Biological Laboratory in Woods Hole, MA, using squid from local waters as a research model. The study will be published in the July 5th issue of the Proceedings of the National Academy of Science.

Herpes virus causes diseases ranging from cold sores to chicken pox. Genital herpes in a woman poses the risk of death to her unborn fetus and to the infant during delivery. Scientists know that in humans the herpes virus initially enters the body through a nerve ending in a mucous membrane, such as the lip. The virus then travels along the string-like nerve to the central nervous system near the brain. There it replicates or lays dormant until stress or some other trigger causes the virus to flare up, resulting in an inflammation (a cold sore, for example) at the original site of entry.

Until this study, no one had observed or recorded the movement of the herpes virus in a living nerve cell, explains Bearer, an associate professor in Brown's Department of Pathology and Laboratory Medicine and a summer investigator at the Marine Biological Laboratory in Woods Hole. Understanding how a virus gets from one place to another within the nerve cell may help clinicians better treat, and perhaps even cure, potentially lethal viral infections.

To track the virus from nerve ending to cell nucleus, Bearer decided to inject the Herpes simplex Type I virus into one of the world’s most thoroughly studied nerve cells: the "giant" axon of the Woods Hole squid. The squid giant axon is so large—about the width and length of a pencil led and a 1000 times wider than that of any other vertebrate—that you can see it with the unaided eye. Scientists can also keep the axon alive for up to six hours after it’s been dissected from the squid, meaning they can watch the virus as its transported from one end of the cell to the other in real time.

Three generations of MBL researchers have used the squid giant axon to shed light on many of the puzzles in neuroscience, many of which involve the transport of organelles and other cargo from place to place within a cell. Today, investigators come to Woods Hole each summer from Argentina and Texas, Germany and Rhode Island, looking to the squid giant axon for clues to diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis, and, most recently, the herpes virus.

To infect the squid axon with the human herpes virus, Bearer stripped the virus of its outer envelope, which normally interacts with cell membranes in humans to release the viral particles. She also genetically labeled a vital component of the virus with a dye called green fluorescent protein. This enabled the scientists to use confocal microscopy to visualize the movement of viral particles within the cell.

The experiment was extremely successful. Bearer determined that the viral envelope is not required for transport. She also found that the virus traveled through the axon at an "enormously" fast and consistent speed of 2.2 microns per second, indicating, says Bearer, that a single transport mechanism is responsible for this movement.

"For a long time, it was believed that herpes traveled back to the central nervous system by infecting other cells in the nerve sheath," Bearer said. The virus does infects these cells, she says, but the new research showed that the virus moves much faster within the axon.

Bearer says that the discovery of a single transport mechanism means that science has one target to hit with drug therapy. It also means that the transport mechanism might someday be used for sending new genes into the central nervous system for therapy.

"Our ability to directly observe the intracellular movements of the virus will enable us to discover the molecules and mechanisms by which herpes gets into the nucleus," Bearer said.

The research team included Bearer, Xandra Breakefield and Deb Schuback of the Massachusetts General Hospital, Boston; Thomas S. Reese of the National Institutes of Health, and Jennifer LaVail of the University of California, San Francisco. The study was funded by the National Institutes of Health and by the Marine Biological Laboratory.

The Marine Biological Laboratory is an independent scientific institution, founded in 1888, that undertakes the highest level of creative research and education in biology, including the biomedical and environmental sciences.