The discovery itself was made possible by a method, refined by Tailor, for cloning the receptors relatively quickly. "The basic technique we are using is to isolate a gene from a cell which is susceptible to the virus and express that gene in cells that are resistant to the virus. If the resistant cell becomes susceptible, we know we've found the gene," said Tailor. While the process sounds simple, successfully isolating receptor genes has, until recently, taken many years of painstaking work. But the method used by Tailor employs a retrovirus as a kind of Trojan horse. A retrovirus containing the susceptibility gene is used to infiltrate the resistant cell and deliver its genetic cargo. The process can be complete in as little as six weeks. "To be able to reliably clone the gene we want in such a short time is a major breakthrough," said Kabat.

The OHSU study lays the groundwork for finding other receptors that help viruses, such as HIV, invade cells and could open up new areas of research into drugs to combat the viruses. Viruses and cells are constantly involved in an elaborate arms race. Cells develop resistance to certain viruses, then the viruses mutate and find a way to enter the cells, then the cells develop resistance again, and so on. The leukemia viruses studied in the Kabat laboratory are mutations of earlier forms of the virus. In the case of leukemia, as with AIDS, mutant forms of the virus are often far more damaging than the original virus they sprang from. So finding the receptor the mutant viruses attach themselves to could be used as a clinical tool.

"By identifying the receptor there is a potential to design drugs that block the virus," said Tailor. "The virus first has to attach to the receptor before it can invade the cell. If we can block that part of the process we could potentially prevent entry of the virus."

Efforts to isolate viral receptors continue in the Ka
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Contact: Henry Sessions
sessionh@ohsu.edu
503-494-8231
Oregon Health & Science University
1-Feb-1999