Jefferson scientists reveal how some types of rabies invade the brain

November 14, 2004

Virologists at Jefferson Medical College have found that certain elements of bat rabies virus genes make the virus more adept at invading the brain.

Bat rabies is an emerging problem in North America. It's different from other rabies viruses: It seems able to reach the brain much more quickly than other strains of rabies, and it takes less virus to initiate the brain infection. In many cases of bat rabies infection, there is no known route of exposure.

The researchers, led by Bernhard Dietzschold, DVM, professor of microbiology and immunology and Matthias Schnell, Ph.D., associate professor and acting chair of biochemistry and molecular pharmacology, both at Jefferson Medical College of Thomas Jefferson University in Philadelphia, analyzed which rabies virus genes from a silver-haired bat might play a role in the virus's ability to infect the brain. To do so, they built the first molecular clone of a rabies "street" virus, akin to the virus found in the wild. They then exchanged the genes of the silver-haired bat rabies virus clone with those of a strain used in a rabies wildlife vaccine and discovered that certain parts - particularly the glycoprotein cover on the virus surface - are responsible for the virus's superior ability to attack the brain. They reported their findings this month online in the Proceedings of the National Academy of Sciences.

According to Dr. Dietzschold, the glycoprotein is involved in the uptake of virus by the cell receptor. He notes that the uptake of the silver-haired bat rabies virus is five times faster than other types of rabies virus from other species, which, he says, might account for its ability to infect the brain so rapidly. They reported their findings online in November in the Proceedings of the National Academy of Sciences.

"We also found that the expression of viral genes and proteins - the replication of the virus - is extremely regulated," he says, which differs from other species. "The virus evades immune system recognition" more so than other strains, he notes, which is a "key factor in viral pathogenesis. This basic information will help us understand how the virus invades the central nervous system from a peripheral site in the body."

Dr. Dietzschold points out that physicians and other health care specialists should be aware that rabies virus is not just a single entity, and may have different methods of infection and spread.

"The classic picture of rabies has been changing in the last few years," he says. "We have new viruses that are phenotypically and genotypically different and which may cause different symptoms - not only the classical symptoms such as hydrophobia and difficulty swallowing. That's not always the case anymore."

He plans to continue to investigate the bat rabies virus's ability to invade the nervous system, and "relevant mechanisms behind the pathogenesis of the virus."
-end-
Other Jefferson authors include Hilary Koprowski, M.D., professor of microbiology and immunology, director of the Biotechnology Foundation Laboratories and the Center for Neurovirology at Jefferson Medical College; Mikhail Prosniak, Ph.D., research instructor, Department of Microbiology and Immunology; Milosz Faber, Ph.D., postdoctoral fellow, Department of Microbiology and Immunology; Kazuhiko Nagao, Ph.D., postdoctoral fellow, Department of Microbiology and Immunology; Amy Rice, technician, Department of Microbiology and Immunology; and Rojjanaporn Pulmanausahakul, graduate student, Department of Microbiology and Immunology.

Thomas Jefferson University

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