MOLECULAR BIOLOGY OF THE ADENOVIRUS
The wild type Adenovirus is a non-enveloped virus comprising a double stranded linear 36 kb genome packaged into an icosahedral protein capsid, of approximately 90-100 nm. Each viral particle has a fiber protein that protrudes from the vertex of the icosahedron, which is attached to a knob region that mediates cell entry. The genome is flanked by two inverted terminal repeat regions of DNA (ITR) and each 5’ end is attached to a 55 kDa terminal protein (TP). The genes comprising the genome can be classed into two categories; Early genes (E1 to E4) and Late genes (L1 to L5), depending on whether they are expressed before or after DNA replication (see diagram one).
Diagram One: Adenovirus Genome
Upon entry into the host cell, the knob domain of the adenoviral fiber protein binds to the coxsackievirus adenovirus receptor (CAR) (or CD46 for group B adenoviruses). Subsequently, the RGD mofif in the fiber domain interacts with αv integrin resulting in endocytosis of the viral particle and the formation of clathrin-coated pits. Once in the endosome, the pH becomes acidic allowing the capsid proteins to disassociate and the release of the virion into the cytoplasm. The microtubular network of the cell then transports the virion to the nuclear pore complex, where the viral particle disassembles and the viral DNA is able to enter the nucleus and replicate. In the early phase, the E1, E2, E3 and E4 proteins mediate the replication of the viral DNA using a combination of viral and host cell proteins. The late phase is marked by the activation of the major late promoter that drives expression of capsid proteins, resulting in viral particle assembly.
