Around 40 million people are infected with HIV worldwide and AIDS is still a growing threat in many countries. This protein could also be targeted in the treatment of haematological cancers, including the various types of leukaemia.

SAMHD1 has been shown to limit the infection of certain immune cells by HIV type 1. It does this by breaking down the building blocks of DNA - deoxynucleoside triphosphates (dNTPs) - which are essential for the virus to replicate itself in cells. Viruses do not replicate on their own, but take over other cells and use them as ‘factories’ for virus production.  If a DNA copy of the virus can’t be made because of a reduced pool of dNTPs, then the virus can’t insert itself into the host genome. Dr Harriet Groom, a researcher from the Division of Infectious Diseases in the Department of Medicine, University of Cambridge, secured funding from the Evelyn Trust to look at the details of this process and improve our understanding of the way this protein works.

“Therapeutic targeting of SAMHD1 has tremendous potential, but we really need to understand it in more detail if we want to exploit it effectively for the treatment of HIV and other conditions. My project has been looking this year at how modulation of SAMHD1 affects the energy factories of the cell – mitochondria - which are very sensitive to the levels of dNTP.  We have been examining mitochondrial function in normal conditions and in HIV infection, which should ultimately help us understand dNTP metabolism, mitochondrial disease and reveal the results that therapeutic targeting of SAMHD1 could have,” says Harriet. “We don’t yet understand the full effect of manipulating SAMHD1 in normal cells – and it’s vital that we do.”

Harriet has been considering some central questions, such as how effective would it be to ‘turn on’ SAMHD1 where it’s not active: the levels of SAMHD1 have been shown to vary in healthy people. Alternatively, if the protein was ‘turned off’ would that improve the immune system’s response to the virus?

“In this one year project, we’ve shown that increasing, or reducing, levels of SAMHD1 certainly affects mitochondrial function and that’s an important step forward. Now I’m applying for funding to validate my observations in other cell types and to systematically look at SAMHD1 variation in people.” 

Harriet’s work is vitally important to the worldwide research effort focussed on HIV and AIDS. Recent news that the modulation of SAMHD1 has been shown to enhance the effectiveness of antiviral drugs serves to show that this is certainly a protein packed with potential.