Protein Starves HIV, Thus Protecting Cells
12 Feb 2012 - A protein called SAMHD1 has been found to starve HIV in cells
so that it cannot do anything, thus making the cell resistant to HIV infection, researchers at NYU Langone Medical Center reported
in Nature Immunology . The authors explained that their discovery could pave the way for new therapeutic research at
halting or slowing the HIV's progression to AIDS .
Research co-leader, Nathaniel R. Landau, PhD., said:
"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."
Landau and team found that dendritic cells containing the SAMHD1 protein are resistant to infection from HIV. They set
out to find out why and how SAMHD1 protects such cells. They hoped to find a way of synthetically applying this protection to other
cells in the human body.
Dendritic cells (DCs) - these are immune cells. They process antigen material and present it on
the surface of other immune system cells.
They believe they now have the answer.
When HIV, or any virus, infects a cell, it takes over that cell's molecular material to replicate - the material being
dNTPs (deoxynucleotide triphosphates). dNTPs are DNA building blocks. When the virus replicates, the subsequent DNA molecule has all
the virus' genes, which goes on to replicate more virus.
The scientists wondered why the hijacking of replicating material did not occur in dendritic cells which contain SAMHD1.
They found that SAMHD1 destroys the pool of dNTPs, literally depriving the virus of any building blocks to make its genetic
data - this process is called nucleotide pool depletion.
Dr. Landau said:
"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."
Consequently, HIV (the most common form of this virus) cannot readily infect cells with this protein. It has to evolve so
that it can replicate in CD4 T-cells, different kind of cells. CD4 T-cells don't have any SAMHD1 and have the dNTPs the virus needs to
replicate its DNA data.
HIV has learnt to evolve so that it avoids attempting to infect immune cells which contain SAMHD1, this making sure the
greater immune system is not alerted. The greater immune system, if alerted, can activate a series of antiviral mechanisms which
destroy the virus.
HIV-2 and SIV - relatives of HIV - have developed VPX (viral protein X), which attacks SAMHD1. These other viruses related
to HIV can infect dendritic cells.
Dr. Landau said:
"Viruses are remarkably clever about evading our immune defenses. 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."
If we can fully understand how SAMHD1 protects cells, we could eventually come up with novel ways to stop HIV's ability to
spread, the authors explained.
Increasing SAMHD1 content in cells, or making sure it is present in cells which don't have any, might be a useful way of
focusing future research, they added. As well as reducing levels of dNTPs in cells which are currently targeted by viruses.
Dr. Landau said:
"Over the past few years, a number of these natural resistance mechanisms have been identified, specifically in HIV,
but some have potential applications to other viruses, as well. This is a very exciting time in HIV research. Many of the virus' secrets
are being revealed through molecular biology, and we're learning a tremendous amount about how our immune system works through the
study of HIV."
Written by Christian Nordqvist
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