Adenoviridae
From Wikipedia, the free encyclopedia
| Adenoviruses | ||||
|---|---|---|---|---|
| Virus classification | ||||
|
||||
| Genera | ||||
|
Aviadenovirus |
Adenoviruses are viruses of the family Adenoviridae. They infect both humans and animals. Adenoviruses were first isolated in human adenoids (tonsils), from which the name is derived.
Adenoviruses are classified as group I under the Baltimore classification scheme. They are medium-sized (60-90 nm), nonenveloped icosahedral viruses containing double-stranded DNA. Adenoviruses represent the largest nonenveloped viruses, because they are the maximum size able to be transported through the endosome (i.e. envelope fusion is not necessary). The virion also has a unique "spike" or fibre associated with each penton base of the capsid (see picture below) that aids in attachment to the host cell via the coxsackie-adenovirus receptor on the surface of the host cell. There are 51 immunologically distinct human adenovirus serotypes (6 species: Human adenovirus A through F) that can cause human infections ranging from respiratory disease (mainly species HAdV-B and C), and conjunctivitis (HAdV-B and D), to gastroenteritis (HAdV-F serotypes 40 and 41). 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 primarily spread via respiratory droplets, however they can also be spread by fecal routes as well.
Contents |
[edit] Genome
The adenovirus genome is linear, non-segmented double stranded (ds) DNA which is around 30–38 Kbp. This allows the virus to theoretically carry 30 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. 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.
This family contains the following genera:
- Genus Aviadenovirus; type species: Fowl adenovirus A
- Genus Atadenovirus; type species: Ovine adenovirus D]]
- Genus Mastadenovirus; type species: Human adenovirus C; others include AD-36
- Genus Siadenovirus; type species: Frog adenovirus
[edit] Replication
Adenoviruses possess a linear dsDNA genome and are able to replicate in the nucleus of mammalian 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. 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 (CAR) 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 specialized motif in the penton base protein interacts with an integrin molecule. It is the co-receptor interaction that stimulates internalization 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 signalling and thus induces actin polymerisation resulting in entry of the virion into the host cell within an endosome.[1]
Once the virus has successfully gained entry into the host cell the endosome acidifies, which alters virus topology by causing capsid components to disassociate. These changes as well as the toxic nature of the pentons results in the release 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.[2] After this the DNA associates with histone molecules. Thus viral gene expression can occur 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 is generated which is alternatively spliced to generate monocistronic mRNAs compatible with the host’s ribosome, 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 three-fold: to alter the expression of host proteins that are necessary for DNA synthesis; to activate other virus genes (such as the virus-encoded DNA polymerase); and to avoid premature death of the infected cell by the host-immune defenses (blockage of apoptosis, blockage of interferon activity, and blockage of MHC class I translocation and expression).
Some adenoviruses under specialised conditions can transform cells using their early gene products. E1a (binds retinoblastoma tumor suppressor protein) has been found to immortalise primary cells in vitro allowing E1b (binds p53 tumor suppresor) to assist and stably transform the cells. Nevertheless, they are reliant upon each other to successfully transform the host cell and form tumours.
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 life cycle 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.
[edit] Adenoviruses in humans
[edit] Adenoviruses in animals
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 also can cause respiratory and eye infections. Canine adenovirus 2 (CAdV-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.[3]
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.[3]
[edit] See also
[edit] References
- ^ Wu and Nemerow (2004). "Virus yoga: the role of flexibility in virus host cell recognition". Trends Microbiol 12: 162-168. PubMed.
- ^ Meier and Greber (2004). "Adenovirus endocytosis". J Gene Med 6: S152-S163. PubMed.
- ^ a b Fenner, Frank J.; Gibbs, E. Paul J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press, Inc. ISBN 0-12-253056-X.
[edit] Sources
Centers for Disease Control and Prevention--National Center for Dieseases--Division of Viral and Rickettsial Diseases, Respiratory and Enteric Viruses Branch
