Adenovirus Genome Structure (ITR, E1, E2A……) and adenovirus assembly

Adenovirus is a non-enveloped, 90-100 nm diameter virus presenting icosahedral symmetry (Figure1A). Human adenovirus, containing a linear, double-stranded DNA genome, which is approximately 36kb, is wrapped in a histone-like protein and has two inverted terminal repeats (ITRs) of 50-200 bp, which act as origins of replication, accompanied by a complex series of splicing. Adenovirus transcription is a two-phase event, early and late, occurring before and after viral DNA replication, respectively (Figure1B). The early transcribed regions are E1A, E1B, E2A, E2B, E3, and E4, which are successively transcribed early in the viral reproductive cycle. The proteins coded for by genes within these transcription units are mostly involved in regulation of viral transcription, in replication of viral DNA, and suppression of the host response to infection. The late transcribed genes are L1-L5, which are transcribed later in the viral reproductive cycle, and encode mostly for proteins that make up components of the viral capsid or are involved in assembly of the capsid. The genes in the adenovirus and their functions are given in the following table 3.

Figure1. Schematic of the adenovirus genome and adenovirus-based vectors. (A) Capsid crystal structure. (B) Adenovirus gene map. Top panel: A simplified map of the adenovirus serotype 5 genome showing the early genes (E1–E4) and the region from which the major late transcript is produced. Middle panel: General structure of an early region 1 (E1)-deleted Ad vector. Bottom panel: General structure of a helper-dependent Ad vector [15].

Table3. Functions of known adenovirus proteins [16].
Adenovirus protein	Functions
Capsid proteins II, III, IIIa, IV, VI, VIII, and IX	Structural proteins
Core proteins V, VII, X	Structural proteins
Terminal protein TP	Structural proteins
IVa2, 52K, L1, and 100K	Encapsidation proteins, assembly of viral capsids
L3 protease	Cleave viral precursor proteins pTP, pVI, pVII, pVIII, and IIIa to produce the mature viral proteins
E1A	Activate transcription of a number of viral genes as well as genes of the host cell
E1B 55K	Bind to and inactivate the transcriptional regulator p53, thus blocking transcription of genes normally activated by p53 and contributing to the suppression of apoptosis
E2A and E2B	Involve in replication of viral DNA
E3 RIDα and E3 RIDβ	Membrane proteins, perform a variety of molecular functions that contribute to inhibiting apoptosis
CR1β	Membrane glycoprotein, modulate the host immune response
E3 gp19K	Membrane glycoprotein, inhibit the insertion of class I MHC proteins in the host-cell membrane, thereby preventing T-cell lymphocytes from recognizing that the host cell has been infected by a virus
E3 14.7K	Protect the virus from host antiviral responses
E4 transcription unit	Involve in regulating transcription of viral DNA