Researchers at University College London (UCL) have discovered the mechanism by which retroviruses like HIV can travel between species and also the biological mechanisms behind the 'jumping genes' which make some monkeys immune.
The researchers will now be using this information to develop a gene therapy treatment for HIV/AIDS in humans.
AdvertisementThe international team of researchers, led by Professor Greg Towers, UCL Infection and Immunity, and funded by the Wellcome Trust, have identified a combination of genes in a species of monkey that protects against retroviruses.
Retrovirus is a predominantly opportunistic family of viruses that can integrate into the host's genome and replicate as part of the cell's DNA.
"HIV causes AIDS and affects around 40 million people worldwide. Research has shown that HIV entered the human population from a chimpanzee retrovirus called SIV early in the 20th century. In order for a virus to successfully cross the species barrier and jump into a new species, it first has to bypass the new host's innate immune system, mediated by a combination of genes and proteins. One such gene, called TRIM5, has been shown to protect certain species from retroviruses - but unfortunately the human TRIM5 gene does not protect against HIV infection," explained Professor Towers.
It was found that a species of Asian monkey called Rhesus Macaques have a sophisticated 'antiviral arsenal' that can protect them against retroviruses.
When the researchers closely examined TRIM5 in this species, they showed that in some monkeys another gene called Cyclophilin has been united to the TRIM5 gene, generating a TRIMCyp fusion.
"Cyclophilin is very good at grabbing viruses as they enter cells. By fusing Cyclophilin to TRIM5, a gene is made that is good at grabbing viruses and good at destroying them. This is the second time that this fusion has been identified - a TRIMCyp gene also exists in South American Owl Monkeys and, until now, this was thought to be an evolutionary one-off," said Dr Sam Wilson, the paper's first author.
He added: "This new research shows that a TRIMCyp has evolved independently in two separate species - it's like lightening has struck twice. It's a remarkable example of convergent evolution, where organisms independently evolve similar traits as a result of having to adapt to similar environments. It also highlights the evolutionary selection pressure that viruses like HIV can apply."
It was further explained by Professor Greg Towers: "The discovery is a compelling example of how 'jumping genes' can shuffle an organism's genetic makeup, generating useful new genes, and it is an exciting possibility for novel treatments for HIV/AIDS.
"About 25 per cent of Rhesus Macaques have the TRIM5 and a TRIMCyp gene, greatly expanding their antiviral arsenal. The others have an immunity, based around TRIM5, that protects them against a different combination of viruses. The gene seems to be evolving to protect the individual species from a range of different virus sequences."
Now the team of researchers are planning to develop humanised TRIMCyp that can inhibit HIV infection by artificially fusing human Cyclophilin and human TRIM5.
"We can then introduce the TRIMCyp into stem cells, using gene therapy technologies, and the stem cells could repopulate the patient with blood cells that are immune to HIV. This work, already underway, could offer a real possibility of novel treatments for HIV/AIDS," said Professor Towers.
The team's findings are published in Proceedings of the National Academy of Sciences (PNAS).