Their research study is being published in the August edition of the prestigious international scientific journal Nature Cell Biology.

"We finally understand how the herpes virus invades cells. That will allow us to more effectively manipulate herpes and other viruses as powerful tools to kill cancer," says Lee, professor of microbiology and infectious diseases, Faculty of Medicine. "This discovery will also help us better exploit these viruses to use in gene therapy."

The study provides a blueprint, mapping the pathway that Herpes Simplex Virus takes when it infects cells. That pathway, known as the Ras pathway, is a major biochemical pathway that controls cell growth. In the majority of cancer cells, this pathway is highly activated, resulting in unrestricted cell growth. Normal cells have a Ras pathway that is tightly controlled.

HSV needs two things to fully invade a cell: its own tools, and an activated Ras pathway inside the cell. Lee's team found that when the herpes virus' own tools of invasion were taken away, the virus only infected those cells with a highly activated Ras pathway. Such a virus would be a cancer-killing virus that leaves normal cells untouched.

Once HSV invades a cancer cell, it takes over the cell's resources to replicate itself. The cell eventually ruptures, releasing virus particles which rapidly infect neighbouring cancer cells.

"Lee's work provides an important link in our understanding of how viruses can be genetically engineered to attack cancer. This research will lead to new generations of more specific oncolytic viruses," says Dr. Robert L. Martuza, M.D., Higgins Professor of Neurosurgery at Harvard University Medical School and Chief of Neurosurgery at Massachusetts General Hospital.

Dr. Martuza is currently leading research into Herpes Simplex Virus as a cancer-killing agent at Harvard University Medical School.

This research follows up on previous work by Lee on another virus, known as reovirus, a naturally occurring virus that targets and destroys cancer cells while leaving normal cells unharmed.

Lee's groundbreaking work on reovirus was published in Science in November of 1998. Since then, Oncolytics Biotech Inc. of Calgary, Alberta has been conducting a Phase 1 Clinical Trial of reovirus involving people with cancer.

"After seeing how reovirus infects cancer cells, I started thinking about other viruses and whether they would attack cancer cells," says Lee. "These findings confirm that we are on the right track with our work on the use of reovirus to fight cancer."

The research is also expected to help physicians provide a much more rapid diagnosis of herpes, and to control herpes infections once they are diagnosed.

Lee's team includes Faris Farassati, D. Pharm., a graduate student, and An-Dao Yang, PhD, a research associate in Lee's lab. This research project is supported by the Canadian Institutes of Health Research. - By Karen Thomas

[Contact: Karen Thomas ]

20-Jul-2001