HIV is an elusive adversary. The virus is so good at fooling the immune system that the quest for an HIV vaccine, or even a countermeasure to resist infections, has spanned two fruitless decades. But maybe a defence has been lurking in our genomes all this time.
Nitya Venkataraman from the University of Central Florida has managed to reawaken a guardian gene that has been lying dormant in our genomes for 7 million years. These genes, known as retrocyclins, protect monkeys from HIV-like viruses. The hope is that by rousing them from their slumber, they could do the same for us. The technique is several safety tests and clinical trials away from actual use, but it’s promising nonetheless.
Retrocyclins are the only circular proteins in our bodies, and are formed from a ring of 18 amino acids. They belong to a group of proteins called defensins that, as their name suggests, defend the body against bacteria, viruses, fungi and other foreign invaders. There are three types: alpha-, beta- and theta-defensins. The last group is the one that retrocyclins belong to. They were the last to be discovered, and have only been found in the white blood cells of macaques, baboons and orang-utans.
In previous experiments, Venkataraman’s group, led by Alexander Cole, showed that retrocyclins were remarkably good at protecting cells from HIV infections. They are molecular bouncers that stop the virus from infiltrating a host cell. The trouble is that in humans, the genes that produce retrocyclins don’t work. Over the course of human evolution, these genes developed a mutation that forces the protein-producing machinery of our cells to stop early. The result is an abridged and useless retrocyclin.
But aside from this lone crippling mutation, the genes are intact and 90% identical to the monkey versions. Now, Venkataraman has awakened them. She found two ways to fix the fault in human white blood cells, one involving gene transfer and the other using a simple antibiotic. Either way, she restored the cells’ ability to manufacture the protective proteins. And the resurrected retrocyclins did their job well – they stopped HIV from infecting a variety of human immune cells.