Two Brigham Young University microbiologists have discovered that ribavirin, an antiviral drug showing promise in the treatment of AIDS, induces production of a protein that appears to inhibit an AIDS-related virus found in cattle.
James A. North and Byron K. Murray have been working with the bovine leukemia virus, or BLV, in cell culture. BLV is a retrovirus and close cousin to the virus that causes AIDS in humans.Results of their research were presented this month in Florida at the annual meeting of the American Society for Microbiology.
Retroviruses, which require RNA to replicate, are dangerous because their properties can be altered by going through a DNA phase. Parts of the genetic coding from the DNA can be incorporated into the retrovirus during the process, creating a cell that can cause disease. Such conditions as luekemia, brain infection and tumors are related to the phenomenon
If scientists can identify the protein involved in the disease-generating viruses, it could be more effective than drugs in treatment, North said.
By giving AIDS-related-complex (ARC) patients this protein instead of a drug, scientists would expect fewer harmful side effects and a greater chance of keeping the virus dormant longer.
ARC is the precursor to AIDS. People with ARC have been infected with the HIV virus, but have not yet experienced the disease symptoms identified by the Centers for Disease Control as AIDS.
Data from the BYU experiments suggest that ribavirin induces one or more proteins to bind to the part of a virus that regulates reproduction.
The compound appears to activate production of a protein that could shut off the deadly virus' regulatory code - effectively setting up a road block in the disease's progression.
"These proteins appear to be stimulated by the presence of ribavirin. We believe there's a lot of potential," North said.
Ribavirin was synthesized in 1972 by Roland K. Robins, former director of the Cancer Research Center at BYU. Robins created the drug while at the Nucleic Acid Research Institute in Costa Mesa, Calif., where he again works under one of its subsidiaries. Hundreds of scientific papers have been written about ribavirin, with a general consensus that it is effective against a wide range of both DNA and RNA viruses.
Other researchers have shown that by administering ribavirin to patients suffering from ARC, they may not develop the full-blown disease, the BYU researcher said.
The Food and Drug Administration so far has approved the use of ribavirin (prescribed as Virazole) for limited use in patients with influenza-A and hepatitis-B, and for use in a lower-respiratory disease that usually affects infants. The California legislature also has approved the use of ribavirin for AIDS patients.
Importantly, ribavirin appears to be less toxic to patients than AZT - one of the few drugs available so far in the United States that appears to help some AIDS patients live longer.
The bovine leukemia virus is an ideal model for testing against experimental AIDS treatments, because its structure and chemical composition are closely related to the human immunodeficiency virus.
HIV devastates the human immune system, leaving victims susceptible to many kinds of opportunistic infections that normally are not life-threatening. Victims infected with HIV are candidates for progression to full-fledged AIDS.
How cows develop the bovine leukemia virus is unknown at this point, said Murray.
"We know that ribavirin inhibits essential steps for these viruses to replicate . . . that they have very unique sequences they go through in order to reproduce."
In the BYU experiment, the scientists use fetal lamb kidney cells infected with the bovine leukemia virus to test drugs.
Although the two scientists believe a protein is inhibiting the virus' ability to reproduce itself, the specific protein hasn't yet been identified.
"We've shown that a protein does bind to the virus," said Murray. "Now we want to know where it is binding. Through our research we're looking to see if the protein binds to the regulatory part of the genome - thereby greatly slowing down the virus' progression."