Human Cytomegalovirus Induces the Expression of the AMPKa2 Subunit To Drive Glycolytic Activation and Support Productive Viral Infection
Diana M. Dunn, Irene Rodríguez-Sánchez, Xenia Schafer, Joshua Munger
Abstract
Viruses are obligate parasites that depend on the host cell to provide the energy and molecular building blocks to mass produce infectious viral progeny. The processes that govern viral modulation of cellular resources have emerged as critical for successful infection. Here, we find that HCMV depends on two kinase isoforms to support infection, CaMKK1 and AMPKa2. We find that HCMV specifically induces expression of the AMPKa2 subunit to induce metabolic activation and drive robust viral replication. These results suggest that HCMV has evolved mechanisms to target specific metabolic regulatory kinase subunits to support productive infection, thereby providing insight into how HCMV hijacks cellular metabolism for its replication, and sheds light on potential viral therapeutic vulnerabilities.