A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online in Nature Immunology.

The finding comes from an international team of researchers including scientists from the University of Rochester Medical Center, NYU Langone Medical Center, several institutions in France – and a graduate student who is a political refugee from Africa and is now at work in a Rochester laboratory, intent on helping his people who have been devastated by the HIV epidemic.

While researchers hope the work will one day lead to a way to make anti-HIV drugs more effective by increasing their potency against the virus, they're also excited about its implications for our knowledge of other pathogens, such as herpes viruses, which use the same machinery within our cells that HIV does to replicate.

"The findings may explain why certain anti-HIV drugs used today are more effective under some circumstances and not others," said Baek Kim, Ph.D., professor of Microbiology and Immunology at the University of Rochester Medical Center and one of three corresponding authors of the paper. "It also provides new insights on how many other viruses that afflict people operate in the body."

The work centers on a protein known as SAMHD1, which is found in white blood cells known as macrophages and related cells known as dendritic cells. Last year scientists discovered that the molecule makes it difficult for HIV-1 to infect macrophages – cells that specialize in gobbling up and destroying invaders like viruses.

Now researchers have discovered that the molecule cuts off the supply line of the raw material that HIV needs to create DNA and replicate. That raw material, dNTP, comprises the building blocks of DNA, and without it, HIV can't recreate its DNA in our cells.

The team found that SAMHD1 destroys most of these building blocks, making it nearly impossible for HIV-1 to replicate itself where SAMHD1 resides – the macrophages. Instead, HIV-1 uses the macrophage as a safe haven, surviving in patients for years as it dodges the immune system as well as the drugs designed to kill it. It's thanks largely to its ability to hide out in the body that HIV is able to survive for decades and ultimately win out against the body's relentless immune assault.

The team also discovered how a protein in the other common type of HIV – HIV-2, which is found mainly in Africa – knocks out SAMHD1. They found that the protein Vpx destroys SAMHD1, clearing the way for HIV-2 to infect macrophages. While scientists have known that HIV-2 needs Vpx to infect macrophages, they hadn't known precisely why.