Structural model of the adenovirus virion

 (From Brown DT, Westphal M, Burlingham BT et al.: Structure and composition of the adenovirus type 2 core. J. Virol. 16:366, 1975, with permission.)

Adenoviruses

The adenoviruses are common pathogens of humans and animals. Moreover, several strains have been the subject of intensive research and are used as tools in mammalian molecular biology. More than 100 serologically distinct types of adenovirus have been identified, including 49 types that infect humans. The family Adenoviridae is divided into two Genera, the mammalian adenoviruses (mastadenoviruses) and the avian adenoviruses (aviadenoviruses). The adenoviruses are named after the human adenoids, from which they were first isolated.

Several adenoviruses can cause respiratory and conjunctival diseases. In addition, a few types of human adenoviruses induce undifferentiated sarcomas in newborn hamsters and other rodents and can transform certain rodent and human cell cultures. There is currently no evidence that adenoviruses are oncogenic in humans, but the possibility remains of interest.

Structure

The adenovirus particle consists of an icosahedral protein shell surrounding a protein core that contains the linear, double-stranded DNA genome.(See figure 1) The shell, which is 70 to 100 nm in diameter, is made up of 252 structural capsomeres. The 12 vertices of the icosahedron are occupied by units called pentons, each of which has a slender projection called a fiber. The 240 capsomeres that make up the 20 faces and the edges of the isocahedron are called hexons because they form hexagonal arrays. The shell also contains some additional, minor polypeptide elements. The core particle is made up of two major proteins (polypeptide V and polypeptide VII) and a minor arginine-rich protein (μ). A 55 kDa protein is covalently attached to the 5′ ends of the DNA.

Protease(P03252 )

Function

Cleaves viral precursor proteins (pTP, pIIIa, pVI, pVII, pVIII, and pX) inside newly assembled particles giving rise to mature virions. Protease complexed to its cofactor slides along the viral DNA to specifically locate and cleave the viral precursors. Mature virions have a weakened organization compared to the unmature virions, thereby facilitating subsequent uncoating. Without maturation, the particle lacks infectivity and is unable to uncoat. Late in adenovirus infection, in the cytoplasm, may participate in the cytoskeleton destruction. Cleaves host cell cytoskeletal keratins K7 and K18.

Adenovirus death protein (P24935 )

Function

Promotes the release of progeny virus from the host cell nucleus by accelerating the lysis and death of the host cell.

Preterminal protein (P03269 )

Function

Protein covalently bound to the viral DNA that acts as a primer for viral genomic replication by DNA strand displacement. Assembles on the viral origin of replication in an initiation complex with viral polymerase, DBP, host NFIA and host POU2F1/OCT1. During initiation, the polymerase covalently couples the first dCTP with Ser-580 of pTP. The terminal protein stimulates the template activity over 20 fold compared to protein-free templates. Neo-synthesized viral genomes are linked to two preterminal proteins, one for each 5' end. These new genomes are encapsidated in the nucleus, and during capsid maturation by viral protease, preterminal protein is first cleaved into intermediary (iTP), then into mature TP. May play a role in host nuclear matrix localization of genomic DNA.

Packaging protein 1 (P03272 )

Function

Component of the packaging machinery which encapsidates the viral DNA into preformed capsids and transcriptional activator of the viral major late promoter (MLP). Binds, along with packaging proteins 2 and 3, to the specific packaging sequence on the left end of viral genomic DNA and displays ATPase activity thereby providing the power stroke of the packaging machinery. The activity of packaging protein IVa2 is stimulated by protein 33K which acts as a terminase. May be the protein that pumps DNA into the capsid powered by ATP hydrolysis. Specifically binds to the 5'-CG-3' nucleotides of the repeats making up the packaging sequence. Component of the DEF-A and DEF-B transcription factors that bind downstream elements of the major late promoter (MLP), and stimulate transcription from the MLP after initiation of viral DNA replication. DEF-A is a heterodimer packaging proteins 1 and 2 and DEF-B is a homodimer of packaging protein 1.

Early E3 18.5 kDa glycoprotein (P68978 )

Function

Binds and retains class I heavy chains in the endoplasmic reticulum during the early period of virus infection, thereby impairing their transport to the cell surface. Also delays the expression of class I alleles that it cannot affect by direct retention. Binds transporters associated with antigen processing (TAP) and acts as a tapasin inhibitor, preventing class I/TAP association. In consequence, infected cells are masked for immune recognition by cytotoxic T-lymphocytes (By similarity).

Pre-protein VI (P03274 )

Function

During virus assembly, promotes hexon trimers nuclear import through nuclear pore complexes via an importin alpha/beta-dependent mechanism. By analogy to herpesviruses capsid assembly, might act as a chaperone to promote the formation of the icosahedral capsid.

Early 4 ORF4 protein (P03240 )

Function

Plays a role in viral alternative pre-mRNA splicing. Activates dephosphorylation by protein phosphatase 2A of host SR proteins and converts their splicing properties. When expressed alone ex vivo, induces p53/TP53-independent apoptosis called cytoplasmic death. May mimic nutrient/growth signals to activate the host mTOR pathway.