A virus lodged in human chromosome 7 is still partially functional and may be causing cancers, say Nikolaus Mueller-Lantzsch and colleagues from the University of Saarland Medical School, Germany in the journal
About one per cent of the human genome has been found to be the remnants of viruses called 'retroviruses'. Retroviruses, such as HIV, insert their genes into the genome of an infected cell, and from there direct the assembly and release of new viruses.
This process appears to have gone wrong many times during the course of human evolution, leaving useless, mutated retroviral genes stranded in the genome. These are called 'human endogenous retroviral elements' or 'HERVs'. Chimps and gorillas have the same HERVs as humans, which mean HERVs must date back to the earliest primates, millions of years ago.
But recently researchers have spotted a family of HERVs whose genes are almost intact. Mueller-Lantzsch's team found one such, dubbed 'HERV-K', in human chromosome 7. Some human cancers, such as testicular cancer, produce large amounts of HERV-K protein. The researchers wondered whether this protein production actually causes the cancer.
"This is a very difficult issue to address experimentally," says Luis P. Villarreal at the University of California at Irvine. Our genomes are so loaded with HERVs, he points out, that it is hard to tell whether their presence in a particular cancer simply represents an accidental reactivation. "There have been a lot of false starts in trying to sort out the role of endogenous retroviruses in human cancers," he cautions.
Mueller-Lantzsch's group went through the HERV-K genes one by one, injecting them into cells that they then grew in the laboratory. When they injected these cells into mice, they found that one of the genes, called '
The researchers then screened the protein coded by this gene -- 'cORF' -- against those present in the human testes. cORF, they found, sticks strongly to another protein, 'PLZF', that binds to the DNA of other genes and activates them.
PLZF inhibits cell growth, and is important in the development of cells in the blood and testes. Obviously, if PLZF were intercepted, it might precipitate uncontrolled cell growth -- leukaemia or testicular cancer -- in these tissues.
Bryan Cullen of Duke University, North Carolina, thinks that this is a surprising result. "cORF is a 'shuttle protein' whose physiological role is to move viral genes around inside the cell," he says. "I can see no reason why it should bind PLZF. ".
"[This is] a very neat idea, but it will obviously require much further work to prove that these genes play a causal role in human cancer," comments Bert Vogelstein of the Howard Hughes Medical Institute, Baltimore.
So far, PLZF malfunction has only been firmly linked to testicular diseases in mice. Nevertheless, Mueller-Lantzsch and his colleagues infer that it is too big a coincidence that HERV-K proteins turn up in so many human cancers. When cORF and PLZF embrace, it looks like the results may be deadly.