Genetic Variation in SAMHD1

Summary

Viruses are everywhere.  They sit there quietly without us noticing or interrupt our lives with anything from feeling slightly off-colour to death. We need to understand how viruses interact with cells. Knowing this can help us comprehend normal cell functions and how things can go wrong. What we find out can also help develop new therapeutics.   I am interested in the proteins in human cells called restriction factors that stop HIV growing. There are still 37 million people infected with HIV and 1 million people die per year, so we still have some way to go.  

I am interested in a molecule called SAMHD1 which became famous because it can stop HIV growing in certain immune cells. It does this by breaking down the building blocks of DNA, stopping the virus genome being made. This also makes it important for copying and maintaining the cell’s DNA. The levels of SAMHD1 an individual has in their cells has been shown to affect how they respond to certain classes of anti-cancer and anti-HIV drugs. Identifying DNA changes that affect SAMHD1 levels or activity could pave the way for personalised medicine in anti-cancer and anti-viral treatments. In this project we have already identified changes in the samhd1 region of the genome in NIHR BioResource volunteers. We don’t know what effect these changes could have. In this follow-up study we are recalling volunteers with certain specific changes to analyse SAMHD1 levels and activity in their cells. We will also test how infectable these cells are by HIV and how well particular anti-HIV and anti-cancer drugs work. This project will link DNA changes with SAMHD1 levels, and how this affects response to anti-HIV and anti-cancer drugs.