Adenoviridae - Overview
Introduction
Adenoviridae are a group of double-stranded DNA viruses with an icosahedral nucleocapsid. Many Adenoviridae have been isolated from mammals and birds, but only a small number of these cause significant veterinary disease. The family consists of four genera: Mastadenovirus, Aviadenovirus, Atadenovirus and Siadenovirus. The Mastadenoviruses include Canine Adenovirus 1 (CAV-1) and Canine Adenovirus 2 (CAV-2), which cause Infectious Canine Hepatitis and respiratory disease respectively. Equine Adenovirus A (also known as Equine Adenovirus 1) is also a Mastadenovirus and causes respiratory signs in horses.
Aviadenoviruses are viruses of poultry and other birds. The genus contains inclusion body hepatitis, quail bronchitis and other avian viruses not associated with a particular disease. The Atadenovirus and Siadenovirus genera contain viruses that until recently were unassigned. These include egg drop syndrome virus and adenoviral splenomegaly of chickens as Atadenoviruses, and turkey haemorrhagic enteritis as a Siadenovirus.
Viral Characteristics
The genetic information of Adenoviridae is conveyed by a single, linear molecule of double-stranded DNA which encodes around 30 proteins. Under the influence of both host and virus-encoded factors, the DNA replicates and is transcribed within the host nucleus, where virion assembly also occurs. Basophilic and/or acidophilic inclusions may therefore be seen in the nucleus of an adenovirus-infected cell.
The virus genome is contained within a non-enveloped icosohedral nucleocapsid, which comprises capsomeres (called hexons) and twelve vertex capsomeres (called pentons). A fibre antigen protrudes from each of the twelve pentons, and this attaches to host cell receptors as well as being a type-specific haemagglutinin. This fibre antigen is a feature specific to the Adenoviridae. The hexon of mammalian adenoviruses contains a cross-reacting group antigen.
Replication
Adenoviruses enter the host cell by means of interaction of the receptor, coxsackievirus adenovirus receptor (CAR), with a domain on the fibre protein called the knob domain. Some reports suggest that MHC molecules and sialic acid residues may also function as adenovirus receptors. This initial interaction is followed by a secondary interaction where a motif in the penton protein interacts with αv integrin, stimulating endocytosis of the adenovirus via clathrin-coated pits. Once inside the cell the endosome acidifies, causing the caspid components of the adenovirus to dissociate and releasing the virion into the cytoplasm. The virus is then transported by the microtubule netwoek to the nuclear pore complex, where the adenovirus particle disassembles and DNA enters the nucleus. Viral DNA associates with histone proteins, and replication begins.
The virus replication process is divided to the early and late phases, which are separated by DNA replication. Genes transcribed in the early phase are are responsible for producing non-structural, regulatory proteins. These regulatory proteins control the expression of host proteins necessary for DNA synthesis, activate other virus genes and help prevent death of the infected cell by host immune defences. Once the early genes prepared virus proteins, replication machinery and replication substrates, the adenovirus genome is able to replicate. A protein covalently bound to the 5’ end of the adenovirus genome acts as a primer, and the viral DNA polymerase then uses a strand displacement mechanism for replication. The late phase of the adenovirus life cycle produces structural proteins in which to pack the new genetic material. The virus can then be release from the cell by lysis.
Transmission
Adenoviruses are stable to chemical and physical agents and adverse pH conditions, allowing for prolonged survival outside of the body. Aerosol transmission in respiratory droplets is the primary route of spread, but faeco-oral transmission is also possible.
References
- Carter, GR and Wise, DJ (2005) A Concise Review of Veterinary Virology, International Veterinary Information Service.
- Fenner, F J et al (1993). Veterinary Virology (Second Edition). Academic Press, Inc.
- Wu and Nemerow, G R (2004) Virus yoga: the role of flexibility in virus host cell recognition. Trends in Microbiology, 12(4), 162–168.
- Meier and Greber, U F (2004) Adenovirus endocytosis. The Journal of Gene Medicine, 6, S152–S163.