Intracellular trafficking of adenovirus: Many means to many ends

The intracellular trafficking of adenovirus capsids has been described mainly through observations of trafficking by capsids from subgroup C adenoviruses in transformed cell lines. The basic elements of the trafficking pathway include high affinity binding of the adenovirus capsid to receptors at the cell surface, internalization by endocytosis, lysis of the endosomal membrane resulting in escape to the cytosol, trafficking along microtubules, binding to the nuclear envelope, and insertion of the viral genome through the nuclear pore. The net effect of this basic pathway is to deliver the adenovirus genome to the nucleus in a highly efficient manner with greater than 80% of the genome reaching the nucleus in approximately 1 h. However, exceptions to this trafficking pattern have been noted, including: (1) variations based on adenovirus serotype; (2) variations based on target cell type; and (3) variations based on cell physiology. This review summarizes the classical adenovirus infection pathway along with the exceptions to that trafficking pathway, providing an overview of intracellular trafficking of adenovirus.