Adenoviridae

Aviadenovirus
Atadenovirus
Mastadenovirus
Siadenovirus

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 classifed as group I under the Baltimore classification scheme. They're 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.

Genome

The adenovirus genome is linear, non-segmented double stranded (ds) DNA which is around 30-38Kbp. 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 KD 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

Replication

Adenoviruses possess a linear dsDNA genome and are able to replicate in the nucleus of mammalian cells using the host’s replication machinery.

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 genes, 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.

Adenoviruses in humans

See Adenovirus infection

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.

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.

References

Sources

Centers for Disease Control and Prevention--National Center for Infectious Dieseases--Division of Viral and Rickettsial Diseases, Respiratory and Enteric Viruses Branch

Viruses

External links

Adenoviruses at the University of Leicester

Adenoviruses General Concepts

DNA virus replication strategies

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