Adenovirus

Abstract

Of the 53 different human adenovirus (HAdV) serotypes belonging to species A-G, a significant number are associated with acute respiratory, gastrointestinal and ocular infections. Replication-defective HAdV-5-based vectors also continue to play a significant role in gene transfer trials and in vaccine delivery efforts in the clinic. Although significant progress has been made from studies of AdV biology, we still have an incomplete understanding of AdV's structure as well as its multifactorial interactions with the host. Continuing efforts to improve knowledge in these areas, as discussed in this chapter, will be crucial for revealing the mechanisms of AdV pathogenesis and for allowing optimal use of AdV vectors for biomedical applications.

Fig. 1

Relative dimensions of nonenveloped viruses whose structures have been studied by X-ray diffraction or cryoelectron microscopy (cryoEM). The adenovirus structure is from Chiu et al. (2001). The structures of reovirus, bluetongue virus, and PRD1 were retrieved from VIPER (Virus Particle Explorer, http://viperdb.scripps.edu). The diameter (dia) of the virions, the number of amino acids in their icosahedral asymmetric unit (IAU) as well as their genome size (KBp) are indicated

Fig. 2

The adenovirus vertex region as visualized in a cryoEM structure. (a) The location and associations of the penton base (yellow), protein IIIa (white), protein VIII (red), and protein VI (orange) are shown based on a recent cryoEM structural analysis of an Ad5F35 vector at 6.9 Å resolution (Saban et al. 2006). The peripentonal hexons, which in the intact virion would surround the penton base, are not shown to reveal the inner capsid proteins. (b) A view from the interior of the capsid

Fig. 3

The secondary structure and functional domains of adenovirus protein VI. A schematic representation of preprotein VI and its nuclear import (NLS1, 2) and nuclear export (NES 1, 2) sites, protease cleavage sites, and hexon binding domains are shown. Depicted in red (residues 36–53) is the predicted amphipathic α-helical domain that mediates membrane disruption. The predicted secondary structure of preprotein VI is shown below (left). Note that residues 34–114 are likely to form four α-helical segments. Consistent with this possibility (right panel), the CD spectra of a recombinant pVI_34–114 protein indicates that its secondary structure is estimated to be 85% α-helix and15% random coil by analysis of the spectrum with the CONTIN software package