Adenoviridae
Adenoviruses are medium-sized, nonenveloped viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of illnesses, from mild respiratory infections in young children to life-threatening multi-organ disease in people with a weakened immune system.
Virology
Classification
This family contains the following genera:- Aviadenovirus
- Barthadenovirus
- Ichtadenovirus
- Mastadenovirus
- Siadenovirus
- ''Testadenovirus''
Diversity
- A: 12, 18, 31
- B: 3, 7, 11, 14, 16, 21, 34, 35, 50, 55
- C: 1, 2, 5, 6, 57
- D: 8, 9, 10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43, 44, 45, 46, 47, 48, 49, 51, 53, 54, 56, 58, 59, 60, 62, 63, 64, 65, 67, 69, 70, 71, 72, 73, 74, 75
- E: 4
- F: 40, 41
- G: 52
- respiratory disease
- conjunctivitis
- gastroenteritis
- obesity or adipogenesis
Structure
Adenoviruses are medium-sized. The virions are composed of one linear piece of double-stranded DNA inside an icosahedral capsid. 240 hexon proteins make up the bulk of the capsid, while twelve penton bases cap the icosahedron's corners. The penton bases are associated with protruding fibers that aid in [|attachment] to the host cell via the receptor on its surface.In 2010, the structure of the human adenovirus was solved at the atomic level, making it the largest high-resolution model ever. The virus is composed of around 1 million amino acid residues and weighs around 150 MDa.
Genome
The adenovirus genome is linear, non-segmented double-stranded DNA that is between 26 and 48 kbp. This allows the virus to theoretically carry 22 to 40 genes. Although this is significantly larger than other viruses in its Baltimore group, it is still a very simple virus and is heavily reliant on the host cell for survival and replication. The genes of adenoviruses can generally be divided into well-conserved sets of transcription units with six early transcription units and one late transcription unit ranging from L1-L5. In addition, adenoviruses also contain two intermediate transcription units named XI and IVa2. To increase the viral gene economy, adenoviruses accommodate genes on both strands of its dsDNA meaning that most of its genome is utilized for coding proteins. An interesting feature of this viral genome is that it has a terminal 55 kDa protein associated with each of the 5' ends of the linear dsDNA. These are used as primers in viral replication and ensure that the ends of the virus' linear genome are adequately replicated.Replication
Adenoviruses possess a linear dsDNA genome and are able to replicate in the nucleus of vertebrate cells using the host's replication machinery. Entry of adenoviruses into the host cell involves two sets of interactions between the virus and the host cell. Most of the action occurs at the vertices. Entry into the host cell is initiated by the knob domain of the fiber protein binding to the cell receptor. The two currently established receptors are: CD46 for the group B human adenovirus serotypes and the coxsackievirus/adenovirus receptor for all other serotypes. There are some reports suggesting MHC molecules and sialic acid residues functioning in this capacity as well. This is followed by a secondary interaction, where a motif in the penton base protein interacts with an integrin molecule. It is the co-receptor interaction that stimulates entry of the adenovirus. This co-receptor molecule is αV integrin. Binding to αV integrin results in endocytosis of the virus particle via clathrin-coated pits. Attachment to αV integrin stimulates cell signaling and thus induces actin polymerization, which facilitates clathrin-mediated endocytosis, and results in virion's entry into the host cell within an endosome.Once the virus has successfully gained entry into the host cell, the endosome acidifies, which alters virus topology by causing capsid components to disband. The capsid is destabilized and protein VI, which is one of the capsid constituents is released from it. Protein VI contains an N-terminal amphiphatic alpha-helix, a helical domain that exhibits both hydrophobic and hydrophilic properties. This amphipathic helix enables the binding of protein VI to the endosomal membrane leading to a severe membrane curvature that ultimately disrupts the endosome. These changes, as well as the toxic nature of the pentons, destroy the endosome, resulting in the movement of the virion into the cytoplasm. With the help of cellular microtubules, the virus is transported to the nuclear pore complex, whereby the adenovirus particle disassembles. Viral DNA is subsequently released, which can enter the nucleus via the nuclear pore. After this the DNA associates with histone molecules already present in the nucleus, which allows it to interact with the host cell transcription machinery. Then, viral gene expression can occur, without integrating the viral genome into host cell chromosomes, and new virus particles can be generated.
The adenovirus life cycle is separated by the DNA replication process into two phases: an early and a late phase. In both phases, a primary transcript that is alternatively spliced to generate monocistronic mRNAs compatible with the host's ribosome is generated, allowing for the products to be translated.
The early genes are responsible for expressing mainly non-structural, regulatory proteins. The goal of these proteins is threefold: to alter the expression of host proteins that are necessary for DNA synthesis; to activate other virus genes ; and to avoid premature death of the infected cell by the host-immune defenses.
Some adenoviruses under specialized conditions can transform cells using their early gene products. E1A has been found to immortalize primary cells in vitro allowing E1B to assist and stably transform the cells. Nevertheless, they are reliant upon each other to successfully transform the host cell and form tumors. E1A is mostly intrinsically disordered protein and contains CR3 domain which is critical for transcriptional activation.
DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery, and replication substrates, replication of the adenovirus genome can occur. A terminal protein that is covalently bound to the 5' end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome.
The late phase of the adenovirus lifecycle is focused on producing sufficient quantities of structural protein to pack all the genetic material produced by DNA replication. Once the viral components have successfully been replicated, the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis.
Multiplicity reactivation
Adenovirus is capable of multiplicity reactivation . MR is the process by which two, or more, virus genomes that have been damaged to the point of nonviability interact within the infected cell to form a viable virus genome. Such MR was demonstrated for adenovirus 12 after virions were irradiated with UV light and allowed to undergo multiple infection of host cells. In a review, numerous examples of MR in different viruses were described, and it was suggested that MR is a common form of sexual interaction that provides the survival advantage of recombinational repair of genome damages.Epidemiology
Transmission
Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of the body and water. Adenoviruses are spread primarily via respiratory droplets, however they can also be spread by fecal routes and via aerosols. Research into the molecular mechanisms underlying adenoviral transmission provide empirical evidence in support of the hypothesis that coxsackievirus/adenovirus receptors are needed to transport adenoviruses into certain naive/progenitor cell types.Humans
Humans infected with adenoviruses display a wide range of responses, from no symptoms at all to the severe infections typical of Adenovirus serotype 14.Animals
is a novel species of the Mastadenovirus genus isolated from Myotis and Scotophilus kuhlii in China. It is most closely related to the tree shrew and canine AdVs.Two types of canine adenoviruses are well known, type 1 and 2. Type 1 causes infectious canine hepatitis, a potentially fatal disease involving vasculitis and hepatitis. Type 1 infection can also cause respiratory and eye infections. CAdV-1 also affects foxes and may cause hepatitis and encephalitis. Canine adenovirus 2 is one of the potential causes of kennel cough. Core vaccines for dogs include attenuated live CAdV-2, which produces immunity to CAdV-1 and CAdV-2. CAdV-1 was initially used in a vaccine for dogs, but corneal edema was a common complication.
Squirrel adenovirus is reported to cause enteritis in red squirrels in Europe, while gray squirrels seem to be resistant. SqAdV is most closely related to the adenovirus of guinea pigs.
Adenovirus in reptiles is poorly understood, but research is currently in progress.
An adenovirus has been identified as the cause of melanistic hyperpigmentation or “blotchy bass syndrome” in black basses.
Adenoviruses are also known to cause respiratory infections in horses, cattle, pigs, sheep, and goats. Equine adenovirus 1 can also cause fatal disease in immunocompromised Arabian foals, involving pneumonia and destruction of pancreatic and salivary gland tissue. Tupaia adenovirus has been isolated from tree shrews.
Otarine adenovirus 1 has been isolated from sea lions.
The fowl adenoviruses are associated with many disease conditions in domestic fowl like inclusion body hepatitis, hydropericardium syndrome, egg drop syndrome, quail bronchitis, and gizzard erosions. They have also been isolated from wild black kites.
Titi monkey adenovirus was isolated from a colony of monkeys.