Children are most likely to have adenovirus infections, but people of all ages can get them. They spread through the air by coughing or sneezing, and through contact with contaminated objects. Symptoms are most often mild and affect the respiratory tract. However, some strains can infect the gastrointestinal tract, causing diarrhea and vomiting.
Human adenoviruses
Several types of human adenoviruses (HAdV) cause infection in humans. They are medium-sized, nonenveloped icosahedral viruses containing double-stranded DNA. Each species of adenovirus is divided into immunologically distinct serotypes. The virus genome contains an early and a late gene segment. The early genes express proteins that activate other virus genes and promote viral DNA replication. After synthesis of the viral DNA, the late gene is transcribed from a major late promoter. The late genes encode the proteins required to assemble virus particles and infect cells.
Adenoviruses can be transmitted by direct contact, fecal-oral transmission, and waterborne transmission. They can also persist in the tonsils, adenoids, and intestines of infected individuals. These persistent infections are usually asymptomatic and can remain latent for months or years. Infection by certain adenoviruses is associated with sporadic and epidemic disease outbreaks including keratoconjunctivitis, urogenital tract infection, and diarrheal illness in children and adults.
Infection by HAdV can lead to a variety of clinical signs and symptoms depending on the virus type and the host immune response. Symptoms range from mild upper respiratory infections to severe diarrheal illness in the elderly.
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Most adenoviruses are classified into seven immunologically distinct species. These are based on the results of serological and other biological properties including sequence similarity, lack of cross-neutralization, pathology, and molecular evolution. Until recently, only a few of the human adenoviruses had been assigned specific species names. However, a phylogenetic analysis of adenovirus nucleotide and protein sequences allowed the unambiguous classification of many of the newer adenoviruses into species.
The human adenoviruses that have been assigned species names are listed in Table 1. Molecular characteristics are provided for each species. In addition, hemagglutination and neutralization assays for each adenovirus are shown.
Animal adenoviruses
Adenoviruses are naturally occurring viruses in a variety of animal species. Some of these viruses can cause a wide range of symptoms in affected animals, depending on the infecting serotype. These diseases can vary from gastrointestinal disease to viral meningitis and hepatitis. Adenoviruses are also known to cause a range of respiratory illnesses, such as bronchiolitis and pneumonia. These diseases can be mild to severe, especially in babies and people with weakened immune systems.
Animal models are indispensable for studying adenovirus pathogenesis and disease progression. They allow researchers to expand on in vitro findings and to study the mode-of-action of anti-infectives and vaccines in physiological settings. They also allow researchers to test for the efficacy of new drugs and vaccines in non-human organisms.
Various animal species have been used as model hosts for adenoviral infection and disease research since the 1950s. These models have been important for identifying key phenotypic characteristics of adenovirus infection, including the phenomenon of persistent infections and viremia. They have also been critical for determining the cellular and molecular mechanisms that are involved in adenovirus persistence and transformation [1].
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The Syrian hamster (Mesocricetus auratus) has been a major animal model for human adenovirus studies since 1962. This medium-sized rodent is very susceptible to a wide variety of DNA and RNA viruses, and has a relatively well-defined genome and host response to infection. Moreover, the genetic tools and reagents required to perform molecular analysis of adenoviral vectors are readily available for this model. Consequently, the Syrian hamster has become the preferred animal model for adenoviral vector-based studies of basic adenovirus biology, tumorigenesis, countermeasure development, and oncolytic vector development [43].
The generation of recombinant adenoviruses can be achieved by homologous recombination in mammalian cells or through in vitro molecular cloning and transfection into mammalian cell lines. Plaque purification is necessary to separate wild-type from recombinant adenoviruses when the latter are generated through homologous recombination in adherent mammalian cell lines. This step is not necessary when adenoviruses are produced using the AdEasy system, in which case recombination takes place in E. coli.
Adenoviral vectors
Adenoviral vectors (AdV) are non-enveloped viral vesicles that contain a linear double-stranded DNA genome and icosahedral protein capsid. They are used in gene transfer applications such as cell biology, in vivo studies, and cancer gene therapy. These vectors are also commonly used in viral vaccine development. They are easy to handle, efficient in transduction, and have high transgene expression. However, they can elicit immune responses. In addition, they can cause inflammatory reactions in the target tissue. These adverse effects can limit the use of AdV vectors in clinical applications.
Several techniques have been developed to reduce the toxicity of adenoviral vectors and improve their packaging capacity. These include the deletion of the virus genes E1 and E3 and the insertion of transgenes into the vector genome. The latter approach requires the construction of a shuttle plasmid that can deliver the foreign gene into the viral genome by homologous recombination. The shuttle plasmid contains a promoter that drives the expression of a desired transgene. The plasmid also has a PacI restriction site (which cuts at TTAATTA) to facilitate linearization and removal of the vector backbone.
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Another advantage of adenoviral vectors is their ability to infect post-mitotic cells. This feature makes them suitable for gene transfer into neurons. Moreover, their non-integrating nature means that they do not alter the host genome or increase the risk of tumorigenesis. Compared to other vectors, they are also more effective in inducing a T-cell response.
Creative Biolabs offers state-of-the-art adenoviral vectors with different design and construction for basic research and preclinical applications. These vectors are based on human adenovirus serotype 5. They are optimized for high-titer viral packaging and high-level transduction of host cells. They can package promoter-transgene-poly A cassettes ranging in size from 8 kb to more than 16 kb.
Adenoviruses are capable of infecting post-mitotic cells and can induce high levels of gene expression. They can also be modified to target specific cells or tissues. For example, the knob region of the adenovirus fiber capsid can be modified to enhance its interaction with surface-expressed integrins on cancer cells. This can lead to a more effective oncolytic effect, which can kill cancer cells.
Adenovirus epidemics
Human adenoviruses cause infections of the upper and lower respiratory tract and the gastrointestinal tract. Some strains can also cause eye infections and genital diseases, but the majority of illnesses caused by these viruses are mild. The viruses can be spread by close personal contact, such as shaking hands and coughing or sneezing. Some adenoviruses also spread through an infected person’s stool and some strains can spread through water, such as swimming pools.
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Most adenoviruses are infrequent causes of disease in healthy people, but they can lead to more serious illness in infants and the elderly or immunocompromised adults. People who are immunocompromised, such as those receiving chemotherapy or who have undergone organ or stem cell transplantation, are at greater risk for developing severe illness from adenovirus infection.
Adenoviruses are usually very contagious. They can spread by respiratory droplets (coughing or sneezing) and through touching an object or surface with the virus on it and then touching the mouth, nose, or eyes before washing one’s hands. Adenoviruses are also resistant to many disinfectants, and they can survive on objects or surfaces for a long time.
There are 52 immunologically distinct adenovirus serotypes that can infect humans. Among them, the most common types are those that cause respiratory illness. Some adenoviruses can establish persistent infections in the tonsils and adenoids of people with weak immune systems, who can then shed the viruses for months or even years. Infectious adenoviruses can also cause diarrheal illnesses, and some strains are associated with infectious diarrheal syndrome in recipients of hematopoietic stem cell transplants.
Infected patients can be treated with rest, plenty of fluids, and over-the-counter medicines to relieve fever or discomfort. Ill persons should be advised to see a doctor if their fever persists for more than a few days or if breathing problems occur. In some cases, the infection may require hospitalization and additional treatment. Antibiotics are generally not used in the treatment of adenovirus infection. Some strains of adenovirus have been found to be oncogenic, but research into their possible human cancer effects has been inconclusive.
