Humans possess a formidable multi-layered defense system that protects us against viral infections. Better understanding of these defenses and the tricks that viruses use to evade them could open novel avenues for treating viral infections and possibly other diseases. For example, a human protein called SAMHD1 impedes replication of the human immunodeficiency virus (HIV) and other viruses by depleting deoxynucleotides -- building blocks needed for the replication of the viral genome. It has long remained a mystery whether and how this protein is activated in response to infection.

Now researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered that SAMHD1 recognizes a unique molecular pattern in nucleic acids. This pattern, called "phosphorothioation," may act as a signal for action. It's like a sentinel atop a palace wall who sees an invading horde in the distance and calls the troops to battle stations. Understanding the mechanism of SAMHD1 activation could be a step forward in the fight against HIV/AIDS.

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