10 Things to Know about Adenoviridae
Adenoviruses might seem forgetful, but there is really a lot going on inside of that icosahedral capsid!

Home 

Viral Timeline

Molecular Biology 

Disease and Treatment

Recent Findings 

Links of Interest & Works Cited 


1) The Simultaneous Discovery of Adenoviruses 

Adenoviruses were first identified by two different groups of scientists independently and basically simultaneously.

One identified adenovirus through the explantation of normal human tissues. In 1953, Wallace Rowe was working with Robert Huebner at the National Institutes of Health on a project to isolate the "virus of the common cold." Rowe was using adenoid and tonsil explants from cell cultures and noted that in some of the adenoid cultures, the cells appeared "rounded and clumped". He investigated this cytopathic effect to see if it was caused by viral infection, identifying the viral agent to be that of adenovirus. The other identification ocurred through the direct collection of the virus from epidemics of acute adenoviral disease.

2) Split Gene Discovery: 1993 Nobel Prize in Physiology or Medicine

In 1993, Richard Roberts and Phillip Sharp were researching adenovirus and discovered a novel genetic trait of this virus, split genes. Specifically, they were examining a hybrid of viral mRNA and its corresponding template DNA with an eletron microscope. They noticed that this mRNA was not encoded in the DNA molecule at hand. Instead, Roberts and Sharp observed  loops of unhybridized DNA (see A, B and C in the picture to the right) and  concluded the the mRNA was not derived straight from a continuous encoded region of the DNA as is usually the case, but rather from four discontinuous segments emphasized by the loops on the viral DNA. Through further research of this phenomenon, they found that segments called exons are retained on the mRNA and the intervening sequences  (A, B, C) called introns are excised or "spliced" out during the process of mRNA maturation.  

3) Adeno-Associated Virus:

Adeno-associated virus or AAV is a single-stranded DNA virus in the family Parvoviridae, genus Dependovirus. It is small, only about 20 nm and replication-defective, meaning that it cannot replicate in a host on its own and must therefore be coupled with another virus to mount a successful infection in a host. This other virus is adenovirus. Specifically, AAV is reliant on several of the adenoviral genes for proliferation. When coupled with adenovirus, AAV can infect both dividing and non-dividing cells as well as incorporate itself into the genome of a host cell. AAV is an orphan virus, meaning that it is not currently associated with disease.

In the image below, the arrow indicates an AAV virion amidst a cluster of adenovirus particles.

 

AAV currently receives a lot of research attention in terms of its potential use in gene therapy. Several features of this orphan virus make it a particularly attractive candidate including its minimal immunogenicity, its lack of pathogenicity on its own and its incorporation into the human genome at a predictable site, namely at chromosome 19. However, there are several drawbacks to the use of AAV in gene therapy including the humoral immune response it can insight in a host and its limited vector cloning capacity.

4) The Unique Shape of the Virus: 

Below is an enlarged picture of the adenovirus particle. As imaged, the viral capsid is icosahedral with 12 fibrous projections sticking out of it, giving adenovirus a distinct, easily-recognizable shape. These projections serve the function of attaching to the surface of the cell that the virus is trying to infect.  

5) Toxic Factor: Penton Base Proteins

The base proteins of the pentons, from which the defining shape-characteristic fibers of the adenovirus extend, contain a  number of toxins.  The virus uses this toxic nature to help in the release of the virion into the cytoplasm of the cell during infection. Then, via the nuclear pore, the viral genome is released into the nucleus of the host cell where it replicates.

6) Oncogenicity:
John Trentin, in 1962, discovered that adenovirus type 12 can cause cancer in baby hamsters. This is not surprising as many DNA viruses have recognizable oncogenic potenital. However, it no link to human cancer has been since identified.

7) Interesting Symptoms: Cervicitis and urethritis 

As discussed in Disease and Treatment, adenoviruses have a variety of clinical presentations. The most well-known symptoms are respiratory disease and gastrointestinal illness.  These are characterized by inflammation of mucous  and intestinal membranes. However, serotypes Ad8, Ad19, and Ad37 in the subgenus D, have been associated not only with keratoconjunctivitis, but have also been isolated from the genitals of individuals with cervicitis, genital ulcers and urethritis. Although relatively rare, this is a unique characteristic of clinical adenovirus presentation, worth while to keep in mind in the development of differential diagnoses. 

8) The Vaccine Story:

 In 1971, a vaccine against adenovirus was introduced to military populations in which the incidence of infection and consequential acute disease had been particularly high. It was a live, non-attenuated vaccine that was administered orally in coated capsules. Attenuation occurred through the route of administration with this vaccine because enteric tract infection is asymptomatic and insights a good antibody response protecting the respiratory tract from future infection. This vaccine proved a terrific success in reducing adenovirus infection rates; however, its use declined when the vaccine needed to be upgraded and the military was unwilling to fund this work. Its production was discontinued completely in 1995 and in 1999, the last stores of vaccine were used up. Not surprisingly, this resulted in an increased incidence of adenovirus infection among military recruits, for example the Ad11 epidemic at a job-training facility in South Dakota.

Further vaccine production research has occurred more recently, namely towards the development of an attenuated vaccine produced by disabling some of the early genes on the viral genome. This vaccine model has been tested in the treatment of cystic fibrosis. 

 

9) Use in an HIV Vaccine:

Adenoviruses have also been employed in vaccine development for other viruses; however, no attempts have proved successful up to this point. Specifically, adenoviruses have been experimented with in HIV vaccine development.

10) Viral Inclusion Bodies:

Like some other viruses, adenoviral infections create viral inclusion bodies in  infected cells. Pictured below (see arrows)