Structural Organization and Protein-Protein Interactions in Human Adenovirus Capsid

Human adenoviruses (HAdVs) are large (150 MDa), complex, nonenveloped dsDNA viruses that cause self-limiting respiratory, ocular and enteric infections. They are significant health hazard in young, elderly and immuno-compromised populations. Moreover, various adenoviruses (AdVs) of mammalian origin are being used as vectors in gene, vaccine and cancer therapies. Multiple copies of at least 13 different proteins, all in all ~2800 protein molecules, come together to form an adenovirus virion packaging the ~36 Kbp geome. The details of structural organization of the adenovirus capsid and underlying network of protein-protein interactions provide clues into designing the modified and novel adenovirus vectors with desired functionalities and/or targeting specificities. The advancements in 3D structure determination by cryo-electron microscopy (cryo-EM) in the past decade have enabled unveiling of the complex organization of adenovirus architecture at near atomic resolution. Specifically, these studies revealed the structures and the network of interactions involving cement/minor proteins in stabilizing the AdV icosahedral architecture, which appear to be mostly conserved among human adenoviruses. In this chapter, we describe the current state of knowledge on the structure and organization of human adenoviruses.