BBC News - 12 February 2012
Scientists have shown how some cells in the body can repel attacks from HIV by starving the virus of the building blocks of life.
Viruses cannot replicate on their own; they must hijack other cells and turn them into virus production factories.
A study, published in Nature Immunology, showed how some parts of the immune system destroy their own raw materials, stopping HIV.
It is uncertain whether this could be used in therapy, experts caution.
HIV attacks the immune system and can weaken the body's defences to the point that everyday infections become fatal.
However, not all parts of the immune system become subverted to the virus' cause. Macrophages and dendritic cells, which have important roles in orchestrating the immune response, seem to be more resistant.
Raw materials Last year researchers identified the protein SAMHD1[Nature 2011 May 25;474(7353):654-7 - SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.] as being a critical part of this resistance. Now scientists believe they know how it works.
They have shown that SAMHD1 breaks down the building blocks of DNA. So if a cell needs to make a copy of itself it will have a pool of these building blocks - deoxynucleoside triphosphates or dNTPs - which make the new copies of the DNA. However, they can also be used by viruses.
The study, by an international team of researchers, showed that SAMHD1 lowered the levels of dNTPs below that needed to build viral DNA and prevented infection. When they removed SAMHD1 then those cells had higher levels of dNTPs and were infected by HIV.
The report said: "By depleting the pool of available dNTPs, SAMHD1 effectively starves the virus of a building block that is central to its replication strategy." It is possible for macrophages and dendritic cells to produce SAMHD1 as they are "mature cells" which do not go on to produce new cells.
Prof Baek Kim, one of the researchers from the University of Rochester Medical Center, said: "It makes sense that a mechanism like this is active in macrophages.
"Macrophages literally eat up dangerous organisms, and you don't want those organisms to have available the cellular machinery needed to replicate and macrophages themselves don't need it, because they don't replicate.
"So macrophages have SAMHD1 to get rid of the raw material those organisms need to copy themselves. It's a great host defence." Dr Jonathan Stoye, virologist at the Medical Research Council National Institute of Medical Research, was part of the team which determined[Nature. 2011 Nov 6;480(7377):379-82. doi: 10.1038/nature10623 - HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.] the chemical structure of SAMHD1 last year and predicted that it would attack the dNTPs.
"We hypothesised that it works in this fashion and the paper tells us we were right. It is depleting cells of these dNTPs, in cells which are not proliferating (dividing)." However, some cells do need to divide to boost numbers as part of the immune defence. Such as CD4 cells which are the prime target for HIV infection.
"Cells which are proliferating would be in trouble if we took dNTPs away," Dr Stoye said.
He added: "How we can use the anti-retroviral action of this protein is not clear to me."