Researchers have discovered a mechanism by which the immune system tries to halt the spread of HIV.
Researchers have discovered a mechanism by which the immune system tries to halt the spread of HIV.
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Harnessing this mechanism, revealed by researchers at NYU Langone Medical Center and colleagues, may open up new paths for therapeutic research aimed at slowing the virus' progression to AIDS.
"A lot of research on viruses, especially HIV, is aimed at trying to understand what the body's mechanisms of resistance are and then to understand how the virus has gotten around these mechanisms," said co-lead investigator Nathaniel R. Landau, PhD, a professor of microbiology at the Joan and Joel Smilow Research Center at NYU School of Medicine.
The research focused on a protein called SAMHD1. Recent studies have found that immune cells, called dendritic cells, containing the protein are resistant to infection by HIV. Since the discovery, scientists have sought to understand how SAMHD1 works to protect these cells, with hopes that science might find a way to synthetically apply that protection to other cells.
Dr. Landau and his team have found that when a virus, like HIV, infects a cell, it hijacks the cell's molecular material to replicate.
That molecular material is in the form of deoxynucleotide triphosphates (dNTPs), which are the building blocks for DNA. Once the virus replicates, the resulting DNA molecule contains all the genes of the virus and instructs the cell to make more virus.
Researchers wanted to understand how cells containing the SAMHD1 protein are protected from such hijacking. They found that SAMHD1 protects the cell from viruses by destroying the pool of dNTPs, leaving the virus without any building blocks to make its genetic information - a process researchers call nucleotide pool depletion.
"SAMHD1 essentially starves the virus. The virus enters the cell and then nothing happens. It has nothing to build and replicate with, so no DNA is made," Dr. Landau said.
As a result, the most common form of HIV does not readily infect these cells. Instead, the virus has evolved to replicate mainly in a different kind of cell, called CD4 T-cells, which do not contain SAMHD1 and therefore have a healthy pool of dNTPs.
Dr. Landau explained that the virus has evolved in such a way that it may deliberately avoid trying to infect immune cells with SAMHD1 to avoid alerting the greater immune system to activate a variety of antiviral mechanisms to attack the virus. Viruses that are related to HIV, like HIV-2 and SIV, have developed a protein called viral protein X (VPX) that directly attacks SAMHD1. This allows the virus to infect dendritic cells, an important type of immune cell.
"Viruses are remarkably clever about evading our immune defenses. They can evolve quickly and have developed ways to get around the systems we naturally have in place to protect us. It''s a bit of evolutionary warfare and the viruses, unfortunately, usually win. We want to understand how the enemy fights so that we can outsmart it in the end" Dr. Landau said.
Understanding the mechanism by which SAMHD1 provides protection to cells may provide a new idea about how to stop or slow the virus' ability to spread, Dr. Landau explained.
The study appears online ahead of print today in Nature Immunology.
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