Human adenovirus type C genome

Reference sequence
Available Adenovirus sequences

Adenovirus transcription cascade

Immediate Early:

E1A is transcribed from the E1A immediate early promoter as soon as the viral genome enters the cell nucleus.

The host cell cycle is pushed into the S phase.


Immediate early to early switch: E1A activates the early promoters

Early:

Initial expression of E1A provides transcriptional activators that, with host proteins, turn on the expression of the early promoters E1B, E2E (E2 early), E3, and E4.

The early proteins optimize the cellular milieu for viral replication, and counteract a variety of antiviral defenses.
The major late promoter (MLP) is weakly active during this phase with a transcription up to L1 (primarily producing the i-leader protein and L1-52/55K proteins).

Efficient transcription from the E2E promoter results in accumulation of the E2A DNA binding protein (DBP), E2B precursor terminal protein, and DNA polymerase, which set the stage for viral DNA replication to begin.

Early to intermediate switch: accumulating pool of viral genomes activates the IVa2 and IX promoters

Intermediate early:

Activation of the transcription from pIX, IVa2, and E2 late promoters.

Transcription of the E4 region declines probably due to the repression by the DNA-binding protein.

Early to late switch: E4orf4 induces late mRNA production . pIX and IVa2 proteins upregulate the transcriptional activity of the major late promoter (MLP) . Expression of L4-22K from L4 promoter activates maximal expression of the MLP . L4-22K and L4-33K regulate the splicing pattern of late transcripts .

Late:

The MLP is fully activated and produces transcripts from L1 to L5 to allows synthesis of structural proteins.

100K protein induces host translation shutoff, late viral transcripts being translated efficiently through ribosomal shunting.

The adenovirus death protein (ADP) encoded by region E3 is expressed early but is greatly amplified at late stages of infection. UXP is also abundantly expressed during the late stages of infection.

Splicing events

Except for the polypeptide IX mRNA, all primary transcripts undergo one or more splicing events which give rise to about fifty distinct mRNAs during the lytic infection .

Encoded proteins

Variation of the E3 region among human AdV species

From: Robinson et al. "Molecular evolution of human species D adenoviruses." Infect Genet Evol. 11:1208-17 (2011).