Cellular infrastructure is often compared to a highly organized city. Organelles act as molecular factories to produce proteins, lipids, nucleic acids and energy (ATP). The distribution of these products throughout the cell is critical to cell viability and function. Due to the density of the host cytoskeleton and cellular organelles, there is a formidable barrier to the free diffusion of macromolecular complexes (protein density in the cytoplasm approaches 300 mg/ml [51], analogous to the viscosity of wet sand). The cytoskeleton provides a highly dynamic, adaptable system that provides mechanical strength to the cell as well as the molecular framework for localized and long-distance trafficking of vesicle cargo and cellular organelles (10). The complex process of traffic control is maintained by three “basic” filament systems: actin filaments, microtubules, and intermediate filaments (IFs)(which provide a scaffold for proteins involved in polarized trafficking)(77). Molecular motor proteins facilitate the movement of various cargoes by hydrolyzing ATP and virtually walking along actin streets and microtubule highways. These active transport mechanisms are crucial to the efficient transport of molecules larger than 500 kDa (54, 55).

The Herpesviridae family, comprising the alpha-, beta-, and gammaherpesvirus subfamilies, is a large and diverse group of double-stranded DNA viruses. Commonly studied members of the alphaherpesvirus subfamily include the human pathogens herpes simplex virus (HSV) and varicella-zoster virus (VZV) and the animal pathogens pseudorabies virus (PRV), bovine herpesvirus, and Marek’s disease virus. The betaherpesvirus subfamily includes, among others, human and mouse cytomegalovirus (HCMV and MCMV, respectively), while the gammaherpesvirus subfamily contains the lymphotropic Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV).