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Scientists found ancient Human Germ Killer

by Medindia Content Team on Mar 21 2002 4:19 PM

A substance that scientists created using information taken from a monkey gene ``dramatically protected'' human cells from the AIDS virus in a laboratory experiment. The researchers believe the substance, which they call ``retrocyclin,'' was once produced naturally in human cells, but was lost to humans because of an ancient mutation.

Alexander Cole, a scientist at the University of California, Los Angeles, medical school, said he and other researchers were led to the mutated human gene for an HIV-inhibiting compound by a sort of natural antibiotic found in the bone marrow of rhesus monkeys. The monkey substance was designated RTD-1.

Such naturally occurring germ fighters, known as ``defensins,'' are believed to have evolved tens of millions of years ago, Cole said, before birds separated from their reptile ancestors. They inhibit not only viruses but bacterial diseases as well. Although human beings have a variety of defensins, the fact that HIV is almost always fatal suggests that none exists for that virus.

Although it is not known if the monkey defensin is the reason these animals can be infected with AIDS-like viruses without becoming ill, the UCLA group became interested in the fact that there appeared to be no comparable human defensin. By scanning the human genome, they found a place where the molecular sequences was nearly 90 percent identical to the monkey gene for RTD-1.

However, inside the human gene was a mutation that prevented it from working, as if an extra, meaningless chain of letters had been inserted at the middle of a long word. Using chemical methods, the UCLA group traced the sequence of the human gene as if the extra letters weren't there and patterned the resulting substance after the monkey RTD-1. These techniques allowed them not only to assemble the chain-like molecule but also to bend it into a circle, then ``fold'' the circle.

Cole said he believes the result is identical to the ancestral human defensin, the one that would have occurred naturally before the mutation appeared. Next they added it to human cell cultures in a laboratory dish and exposed the cells to HIV. The virus was ``dramatically'' inhibited, they reported.

``I have to emphasize that these things are done in cell culture,'' Cole said last week. ``We're a long way from putting these things into humans. We are not even ready to do animal studies. We are looking forward to that in the near future.'' He added: ``I truly believe this molecule has a lot of promise.''

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