The researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered that a human protein named SAMHD1 recognizes a unique molecular pattern in nucleic acids. This pattern, called ‘phosphorothioate’, may act as a signal for action to the human body defense system and henceforth could be a step forward in the fight against HIV/AIDS. The study compares the process to a sentinel atop a palace wall who sees an invading horde in the distance and calls the troops to battle stations. Humans possess a formidable multi-layered defense system that protects us against viral infections. A 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. Understanding the mechanism of SAMHD1 activation could be a step forward in the fight against HIV/AIDS.