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


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 .


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

Type Protein name Function
Capsid shell Hexon protein T=25 icosahedral capsid, Microtubular inwards viral transport
Penton protein T=25 icosahedral capsid, Viral attachment to host host entry receptor, Clathrin-mediated endocytosis of virus by host
Fiber protein Viral attachment to host adhesion receptor
Hexon-linking protein IIIa Cement protein, Hexon stabilization
genome packaging
Pre-protein VI, Endosome lysis protein, Protease cofactor Pre-protein VI: Scaffolding of icosahedron/Nuclear capsid assembly?
Cement protein, peripentonal hexons stabilization
Endosome lysis protein: Viral penetration via permeabilization of host endosomal membrane
Protease cofactor: Virion maturation
Hexon-linking protein VIII Cement protein, peripentonal hexons stabilization
Hexon-interlacing protein IX Cement protein, hexons stabilization
Viral penetration into host nucleus
Packaging protein 1/IVa2 Present at a single vertex
Core proteinsProtease Virion maturation
Core-capsid bridging protein V Binding of the viral genome and the proteins VI and VIII thereby fixing the DNA to the capsid shell
Nuclear capsid assembly?
Histone-like nucleoprotein VII Histone-like nucleoprotein, DNA binding/condensation
Core protein XNucleoprotein, DNA binding/condensation
Replication proteins Terminal protein Strand displacement replication (DNA synthesis priming)
DBPStrand displacement replication (DNA unwinding)
PolymeraseStrand displacement replication (DNA synthesis)
33K proteinViral alternative splicing
Packaging Packaging protein 1/IVa2 Packaging (ATPase motor)
Packaging protein 2/22K proteinPackaging
Packaging protein 3/52KPackaging
33K proteinPackaging (Terminase)
Host-modulation proteinsShutoff protein 100KHost translation shutoff., Ribosomal shunting, Scaffolding (hexons trimerization)
Early E1A 32 kDa proteinG1/S host cell cycle checkpoint dysregulation by virus, cell transformation, Inhibition of host transcription initiation, Inhibition of STAT1 activity
E1B 19 kDa protein Inhibition of host apoptosis by viral BCL2-like protein
E1B 55 kDa protein (TP53_E4-Orf3_E4-Orf6_PML)Inhibition of p53 and E1A-induced apoptosis during the oncogenic transformation induced by the virus
E3 12.5k proteinUnknown
E3 CR1-α proteinapoptosis modulation (cell survival) by TRAIL downregulation and/or ER regulation
E3 18.5 kDa glycoprotein (gp19K)MHC escape: Inhibition of host tapasin by virus
Adenovirus death protein / CR1-βcell lysis
E3 RIDα proteinApoptosis modulation (cell survival) by down-regulation of the TNF-family death receptors
E3 RIDβ proteinApoptosis modulation (cell survival) by down-regulation of the TNF-family death receptors
E3 14.7k proteinInhibition of host NF-kappa-B?
E4 ORF1 protein?tight junction modulation? PDZ protein binding?
E4 ORF2 proteinUnknown
E4 ORF3 proteinPML bodies inhibition
E4 ORF4 protein?alternative splicing?
E4 ORF 34k proteinNuclear innate immunity inhibition,PML bodies inhibition?
E4 ORF6/7 control proteinswitch to intermediate phase, G1/S host cell cycle checkpoint dysregulation by virus
I-leader proteinUnknown
U exonunknown

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).