Adenoviruses infect many species and tissue types, but their human hosts mount effective defenses that normally limit their pathological effects. Host defenses function effectively in healthy individuals; nevertheless, some serotypes can cause considerable morbidity among the immunologically or nutritionally compromised.
A thorough understanding of the adenovirus and particularly the adenovirus structure and function is integral to further research and is explained in detail below.
Adenovirus Structure and Function
The principal component of the complex adenovirus icosahedral capsid is the homotrimeric hexon, of which there are 240 on its facets and edges with the pentons consisting of bases and extended fibers on the 12 apices. Six more structural components can be found in the adenovirus core, five of which are linked to the double-stranded deoxyribonucleic acid (DNA) genome. The final component is the 23K virion protease, which is vital to its assembly. Most explicit structural analyses have been on human serotypes. This is the basic adenovirus structure.
Core structural proteins interact with the DNA to keep the virus template available for at least in vitro replication. Following endocytosis and disruption of the endosome, multiple signals govern entry of the virus core into the host cell nucleus through the microtubule network by the microtubule organizing center. There may be a number of routes for the invading virus template to reach the nucleus. After importation, cellular proteins act to alter template properties, and a template-activating factor remodels the virus chromatin.
Protein V seems to target both nucleus and nucleolus to redistribute nucleolin and B23, an acidic protein and a template-activator, from nucleolus to cytoplasm. B23 seems to interact with both proteins V and pre-VII, perhaps facilitating dissociation of core proteins and exposing the virus template for replication or transcription. Further, a nucleolar component “upstream binding factor” seems to participate in virus DNA replication. The small core protein Mu can duplicate these nucleolar functions. This small peptide can target the nucleolus exclusively and act as a precursor in modulating expression of early proteins and shifting late protein expression. A precursor molecule, polypeptide X, presumably condenses the virus prechromatin and following cleavage by the virion protease a conforming change facilitates packaging of the adenovirus core complex.
The adenovirus’ hexon capsomere is a pseudo-hexagonal trimer on the icosahedral capsid made by triple twists of two beta-barrels at the foundation of every hexon molecule. The pseudo-hexagonal base provides for close arrangement within the facets. Three tower zones present to the exterior. 240 hexons of four kinds can be found in the capsid.
Hexon molecule size can vary by serotype. There are as many as nine hypervariable regions in each hexon molecule located at the top, six apparently as alpha-helical rods related to hexon type-specific antigens with one conducting the major virus negating activity.
At the base of every molecule are one loop and two “jelly rolls” of eight strands which interact with adjacent capsomeres, probably by residual charges in the loops.
Two proteins, the homopentameric base and the homotrimeric fiber emanating from the 12 icosahedron vertices, compose the covalent penton capsomere complex. Three separate sections, knob, shaft, and tail, make up the fiber.
The fiber polypeptide binds noncovalently at its N-terminus to the upper area of the base of the penton. A sequence close to the N-terminus highly consistent among serotypes rests in a furrow on the upper area of the base around two neighboring monomers. Bonds of hydrogen and a salt bridge aid in the consistency of the synergy with the penton base. The peptide sequences are also common in this interconnection among serotypes. The symmetrical mismatch here seems to come from conformational altercations succeeding fiber binding, allowing for only the three fiber peptides on the base with those three malleable tails forming the characteristic trimeric fiber.
Polypeptide IIIa is present in the capsid below the penton base as characterized by difference mapping. The highly helical N-terminal region attaching to the penton base associates with hexons and protein VI and may bind to core proteins V and VII. There seem to be 60 monomers per virion consistent with the interaction of five helical arrays with the remaining capsomeres at the capsid apex.
Polypeptide VI incorporates two elongated alpha-helices, one of which binds to the hexon inside a depression at its base; however, stoichiometry reports imply a count of roughly 360 per virion. But VI affiliates with IIIa at the apices, so there may be multimers of VI or limited occupancy of the hexon pocket.
Polypeptide VIII has proven to be hard to locate, but analysts now agree that it may be found on the inside of the capsid in a ring surrounding the peripentonal hexons and in additional rings around three stabilizing axes. Near the top of the virion, VIII binds the peripentonal hexons and the remainder of the capsid. This may rupture when the penton base detaches during entry of the virus into the cell, releasing H1 hexons and leaving a hexon shell. The extant formational polypeptides associate with the virus genome and the root polypeptides are visible by negative staining electron microscopy but only as diluted matter. This concludes the basic adenovirus structure and function.
On adenoviral infection, the host responds innately to repel the invader. This early response does not depend on transcription of any virus genes. The nature of the response varies according to receptor usage and cell type, a complex cascade with various outcomes. Many response pathways eventually lead to production of interferon. Induction of interferon also can occur after transcription of early genes.
Information from Adenovirus.com
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