Viral exploitation of Mg transport pathways to facilitate replication.

Magnesium (Mg) is essential for all life. Mg binds to nucleic acids and is required for hundreds of metabolic enzymes. Mg levels inside of cells are controlled by multiple transport mechanisms that sense the levels of Mg. Work from our group has shown that the Mg sensors (called CNNMs) form complexes with another class of protein called tyrosine phosphatases (PRLs). Together these PRLCNNM complexes respond to various stimuli including growth factors to sustain Mg levels. It has long been known that Mg can enhance the replication of several virus types including Adenovirus (Ad), Vesicular Stomatitis Virus (VSV) and poliovirus, however, it is not known how viruses can stimulate Mg intake to enhance viral replication. Our findings have shown that viruses exploit the PRL/CNNM system to enhance virus replication. Remarkably, several studies suggest that exploitation of the PRL/CNNM system may widely targeted by diverse range of virus types. In the current proposal we take the first steps to examine how human adenovirus and and Human Immunodeficiency Virus (HIV) modulate Mg transport during infection.