Biomedical Frontiers: Winter 1994, Vol.1, No.2
Beth Levine: Exploring New Antiviral Strategies

When Dr. Beth Levine was doing her fellowship in a laboratory at Johns Hopkins, she and collaborators unexpectedly found that antibodies could control viral gene expression. Now, as an assistant professor of medicine and head of her own laboratory at Columbia-Presbyterian Medical Center, Dr. Levine is continuing to study this phenomenon and to conduct other research that could lead to new types of antiviral therapy.

When the antibody finding was first published (Science, Vol. 254, Nov. 8, 1991, p. 856), it was significant because scientists had previously thought that antibodies acted by neutralizing viruses extracellularly and that intracellular viruses were destroyed by T cells acting on infected cells. She and the laboratory team found, however, that antibodies to the alphavirus envelope glycoprotein inhibit gene expression of the virus inside mice neurons. Dr. Levine is currently studying how the antibodies regulate viral gene expression and how, they might, therefore, treat viral infection.

Another research area in Dr. Levine's laboratory follows up on a finding published in Nature (Nature, Vol. 361, Feb. 25, 1993, p. 739) dealing with the potential antiviral application of bcl-2, an anti-apoptosis cellular oncogene. She and colleagues found that the Bcl-2 gene product protected a mouse adenocarcinoma cell line from undergoing lytic replication and cell death after alphavirus infection. "Our data demonstrate that Bcl-2 promotes viral persistence by counteracting a cell suicide pathway initiated by a viral infection," says Dr. Levine. She adds, "Prevention of virus-induced cell suicide may represent a new approach to treating viral infections." Besides studying Bcl-2, Dr. Levine is studying pharmacological agents that inhibit apoptosis in infected animals and the role of other cellular genes in virus-induced cell death.

Alphaviruses are a group of mosquito-borne RNA viruses that cause acute encephalitis in North America and acute arthritis in Northern Europe, Asia, Africa, and the South Pacific. They are closely related to flaviviruses, a group of viruses that cause more than 100,000 cases of encephalitis a year in Asia. Mosquito-borne encephalitis has a 30 percent overall mortality rate. Presently, there is no treatment available.