Adenoviruses are common pathogens that can cause a range of illnesses in humans, including respiratory infections, conjunctivitis, and gastroenteritis. Understanding their structure is important for comprehending how these viruses interact with host cells to cause infection. This knowledge also aids in developing strategies to combat them, such as in gene therapy applications or vaccine development.
Overall Architecture
Adenoviruses are non-enveloped viruses, lacking an outer lipid membrane. Their defining structural characteristic is an icosahedral capsid, a protein shell with 20 triangular faces. This protein shell encases the virus’s double-stranded DNA genome. The entire virion measures approximately 90-95 nanometers in diameter from vertex to vertex.
The capsid is an assembly of various protein components. Inside this protective protein shell lies the viral core, containing the virus’s genetic material. This core plays an important role in the virus’s life cycle. The overall design provides both protection for the genetic material and the necessary machinery for initiating infection.
Major Capsid Components
The outer shell of the adenovirus is formed by three major capsid proteins: Hexon, Penton Base, and Fiber. Hexon is the most abundant protein, making up about 60% of the virion’s total mass. There are 240 hexon trimers, which form the 20 triangular facets of the icosahedral capsid. These hexon proteins have a pseudo-hexagonal base and are highly stable.
The Penton Base proteins are located at the 12 vertices of the icosahedron. Each vertex is formed by a pentamer of penton base proteins. Extending outward from each penton base is a trimeric Fiber protein.
The fiber protein has a shaft that projects the C-terminal globular head, or knob, away from the virion. This knob domain attaches the virus to specific receptors on host cells, initiating infection. The penton base also contains an Arg-Gly-Asp (RGD) motif on a flexible surface loop, involved in binding to cellular integrins, further aiding in cell entry.
Internal Core Components
Within the protective capsid of the adenovirus lies the viral core, a complex of the double-stranded DNA genome and several associated proteins. The linear double-stranded DNA genome of human adenoviruses can range in length from approximately 26 to 48 kilobase pairs (kbp). This genetic material is tightly packaged within the capsid, a feat that involves compacting a DNA molecule approximately 12 micrometers long into a space less than 100 nanometers in diameter.
The DNA is not naked but is intimately associated with highly basic viral core proteins, which account for roughly 50% of the core’s molecular weight. These include protein VII, protein V, and mu protein (also known as protein X). Protein VII is the most abundant core protein, and it functions to condense the viral DNA, similar to how histones condense eukaryotic DNA.
Protein V acts as a bridge, connecting the viral core to the inner surface of the capsid, interacting with other capsid proteins like protein VI and protein VIII. Mu protein also binds to viral DNA and contributes to genome condensation. The precise organization of these internal components within the non-icosahedral core remains an active area of research, with some studies suggesting a fluid, disordered arrangement of condensed nucleoprotein bundles. The terminal protein (TP) is also part of the core, covalently attached to each 5′ end of the viral DNA, playing a role in DNA replication.
Minor Capsid and Accessory Proteins
Beyond the major capsid and core components, adenoviruses incorporate several minor capsid and accessory proteins that play specialized roles in their structure and infectious cycle. Protein IX is a minor capsid protein located on the exterior of the capsid, functioning as a “cement” protein to stabilize the hexon shell. It helps to glue together the central hexons within each facet.
Protein IIIa and protein VIII are also considered minor capsid proteins, located on the inner surface of the capsid, contributing to the stability of the overall structure. Protein IIIa is involved in capsid assembly and genome packaging.
Protein VI, another minor capsid protein, is intimately associated with the penton base on the capsid interior. It plays multiple roles, including acting as a cofactor for the adenovirus protease, functioning as a chaperone for nuclear transport, and being essential for virus assembly and endosome lysis during cell entry. The viral maturation protease, also known as the adenovirus protease (AVP), is a 23 kDa protein that cleaves several precursor proteins in the virion, including pIIIa, pVI, pVII, pVIII, mu, and the precursor terminal protein, which is a process known as maturation. This proteolytic processing is essential for the virion to become infectious and to enable proper disassembly and release of the viral contents once inside a host cell.