Redefining chronic viral infection

Viruses that cause chronic infection constitute a stable but little-recognized part of our metagenome: our virome. Ongoing immune responses hold these chronic viruses at bay while avoiding immunopathologic damage to persistently infected tissues. The immunologic imprint generated by these responses to our virome defines the normal immune system. The resulting dynamic but metastable equilibrium between the virome and the host can be dangerous, benign, or even symbiotic. These concepts require that we reformulate how we assign etiologies for diseases, especially those with a chronic inflammatory component, as well as how we design and interpret genome-wide association studies, and how we vaccinate to limit or control our virome.