The "Adenoviridae" family of viruses cause a variety of clinical symptoms, from "pink eye" (pharyngoconjunctival fever) to diarrhea (gastroenteritis). While these are not normally life-threatening diseases, Adenoviruses have made their name in the science world as the source of numerous discoveries relevant to all of biology. In the early 1960's, it was shown that Adenoviruses have the ability to transform rodent cells in culture. This fact brought them to the forefront of molecular biology research, which was at that point a very young field. As a result, Adenoviruses have provided many of the first discoveries of important and common biological processes. These discoveries include: splicing of RNA transcripts, the role of proteins for primers of initiation in DNA replication, and the mechanisms of protein targeting. These topics have also generated numerous techniques, including those that study the regulation of transcription in eukaryotic cells. Interestingly, the molecular biology techniques for which these viruses served as models are now being used clinically to treat a variety of diseases.
In 1953, W. Smith and colleagues isolated the first causative agent of acute respiratory illness in humans -- the influenza virus. For the next two decades, epidemiological studies demonstrated the prevalence and importance of this disease, and as a result, researchers directed their efforts towards finding other etiological agents. Twenty years later, in 1953, W.P. Rowe and colleagues dropped a bombshell on the scientific community. While looking for the "common cold virus", these researchers noticed cytopathic effects (such as rounding) of cultured human tonsil and adenoid cells. This observation led them to isolate what was a unique causative agent of acute respiratory disease in humans (hence to name of the family -- adenos, which is latin for 'gland'). Almost simultaneously, in 1954, another group of researchers, including Hilleman and Werner, independently isolated a different causative agent from the cultured human tracheal cells of army recruits. This agent was believed to be the cause of a disease that they called "influenza-like illness", or alternatively, ARD, for Acute Respiratory Disease. In the same year, Huebner, et. al. noticed the association between these viruses and, the family of viruses was born. Today, at least 41 different antigenic types of Adenoviruses have been found to infect humans. The current classification system (described in Taxonomy and Epidemiology) was adopted in 1956.
Several years later, in 1962, JJ Tentin and others discovered that viruses can induce tumors in animals (in this case, cultured rodent cells). This 'oncogenic potential' has extraordinary significance. While adenoviruses have not been conclusively linked to any human cancers, several other viruses, including Epstein-Barr virus, several Human papilloma viruses, human T-cell lymphotropic virus, and HBV, are now recognized as critical etiological agents of specific human cancers. Moreover, the recognition of the importance of this discovery led many scientists to direct their research towards an understanding of these events. In turn, Adenoviruses have been at the forefront of important advances in molecular biology. These will be discussed in Replication and Molecular Biology.
Adenoviruses contain a linear double-stranded DNA genome of about 36 kilobases. Both strands of the genome encode proteins; together, they encode approximately 30 proteins which are transcribed in 3 kinetic classes (immediate early, early, late). The processes of viral DNA replication, mRNA transcription, as well as the assembly of the virion, occur in the nucleus. Viral transcription utilizes cellular RNA polymerase II, while viral DNA replication utilizes a virally encoded protein primer, DNA polymerase, and DNA binding protein, as well as cellular factors. The genome is encased within the capsid, which is an icosahedron made up of 252 capsomers, forming 20 triangular faces, and measuring approximately 70-90nm in diameter. There are 240 "hexons", or clusters of six proteins, and 12 "pentons", or clusters of five proteins. From the 12 vertices of the icosahedral capsid extend twelve fibrous glycoproteins, called "fibers". At the end of each fiber is a knob shaped protein. For a visual image of this structure, please see Images.
Created: February 11, 1999
Last modified: March 5, 1999