A University of Utah researcher is working with two California scientists studying various drugs that could eventually help combat the deadly AIDS virus.
Dr. Raymond F. Gesteland, co-chairman of the department of human genetics and an investigator of the Howard Hughes Medical Institute at the U. School of Medicine, will be exploring molecular mechanisms for the expression of viral, or cellular, genes.His hope is to decipher the life cycle of the HIV virus and, ultimately, impede it.
Gesteland's cooperative work is funded by a $6.5 million five-year grant from the National Institute of Allergy and Infectious Diseases. The project is part of a new federal program, National Cooperative Drug Discovery Groups for the Treatment of Acquired Immune Deficiency Syndrome.
"NIH's new cooperative drug program was designed specifically to encourage the screening of drugs that might be useful in combating the AIDS virus," he said. "Our work at the molecular level may be a long shot as a therapy for AIDS, but it's important that these mechanisms be examined.
"Whether or not the research produces effective new AIDS drugs, we expect to learn more about this class of viruses, which has been implicated in cancer."
The cooperative study between Gesteland and scientists at the University of California at San Francisco and Stanford University is a two-pronged assault on the AIDS epidemic.
"There are three ways the scientific community can attack AIDS," the Utahn said. "One is to look at it epidemiologically. The second way is to mount a crash campaign to develop drugs.
"And finally, scientists can try to understand the virus. Our research is primarily the latter approach, but includes developing assays for finding effective drugs."
The U. geneticist said retroviruses, including the HIV virus, use a peculiar mechanism of protein synthesis in the expression of genes. This mechanism - called frame shifting - is an alteration in the normal readout of the genetic material of these RNA-containing viruses. HIV and most other retroviruses require frame-shifting events in order to grow.
"We aren't working specifically with the AIDS virus, just with frame shifting - that particular mechanism of genetic expression that's peculiar to retroviruses," Gesteland said. "Beginning with systems other than HIV - bacteria, for instance - can we find drugs that will alter the ease with which frame shifting occurs?"
Using readily available drugs that are known to inhibit protein synthesis, the Utah team will test frame shifting in bacteria, yeast and cultured human cells, concentrating on developing several potential assays for drugs that affect the ability of a short sequence of HIV RNA to shift ribosomes into an alternative reading frame.
"The assays we're developing will be safe, because they do not require the use of infectious HIV," said Gesteland. "While these early assays will be removed from the context of HIV in its natural host, we hope in the future that this will lead others to conduct additional tests of promising compounds in retrovirus-infected cells and animals."