Human Adenovirus Gene Expression and Replication Is Regulated through Dynamic Changes in Nucleoprotein Structure throughout Infection

Human adenovirus (HAdV) is extremely common and can rapidly spread in confined populations such as daycare centers, hospitals, and retirement homes. Although HAdV usually causes only minor illness in otherwise healthy patients, HAdV can cause significant morbidity and mortality in certain populations, such as the very young, very old, or immunocompromised individuals. During infection, the viral DNA undergoes dramatic changes in nucleoprotein structure that promote the rapid expression of viral genes, replication of the DNA, and generation of thousands of new infectious virions—each process requiring a distinct complement of virus and host-encoded proteins. In this review, we summarize our current understanding of the nucleoprotein structure of HAdV DNA during the various phases of infection, the cellular proteins implicated in mediating these changes, and the role of epigenetics in HAdV gene expression and replication.