Adenoviruses are medium-sized (90 to 100 nanometers) viruses that contain double-stranded deoxyribonucleic acid (DNA). DNA consists of two strands of a series of nucleotides shaped like a twisted ladder. This structure is referred to as a double helix, and it contains an individual's genetic code.
Adenoviruses were first described in 1953 but were not named until 1956 when they were found to occur in the adenoids. To date, 49 distinct types of adenoviruses have been linked to human infection and more than 120 adenoviruses are known to infect mammals, birds, and reptiles. Each of these viruses produces a unique immune response. Therefore, if an individual develops immunity to one type of virus after an infection, he or she can still become infected with one of the other types. Adenoviruses are unusually stable and can survive for prolonged periods outside the body.
Adenoviruses often cause respiratory illness but may also cause other diseases, such as gastroenteritis (an intestinal infection that may cause diarrhea), conjunctivitis (an infection of the eye surface), cystitis (a bladder infection), skin rash, and meningitis (an infection of the membranes surrounding the brain and spinal cord). The degree of infection ranges from mild to severe. For example, an adenovirus-caused respiratory infection may range from a mild cold to pneumonia. Major complications, such as pneumonia and meningitis, are more likely to occur in patients with a compromised immune system, i.e., patients with HIV/AIDS or patients receiving chemotherapy for cancer.
Adenoviral infections are much more common in children than adults and are responsible for 10% of acute respiratory infections in children. They are also a common cause of diarrhea in this age group.
The adenovirus has been used extensively as a vector in gene therapy. Vectors are organisms that transfer a disease from one organism to another without becoming infected themselves. Adenoviruses are ideal vectors because of their ability to efficiently transfer genetic material from one cell to another. Gene therapy is a process by which genes are injected into the bloodstream to treat a disease. The goal of gene therapy is to replace a defective gene with a normally functioning one. For example, if a cell that normally produces insulin cannot produce it because of a defective gene, the injected gene can perform that function.
Gene therapy at appropriate dosage and usage appears to be both safe and effective. Side effects of adeno-associated vectors appear to be caused by a combination of the vector choice, the vector dose, and the specific product produced for the therapy. Side effects that have been reported with gene therapy include liver damage, nausea, mental confusion, and a drop in blood cell count.
Gene therapy with adeno-associated vectors has potential to treat a wide variety of diseases, such as heart disease, cancer, and cystic fibrosis.
AAV vectors, acute respiratory disease, adeno-associated virus vectors, ARD, cancer, cystic fibrosis, gastroenteritis, gene therapy, genetic disease, meningitis, respiratory infection.
types of the disease
To date, 49 distinct types of adenoviruses have been linked to human infection and more than 120 adenoviruses are known to infect mammals, birds, and reptiles. Each of these viruses produces a unique immune response. Therefore, if an individual develops immunity to one type of virus after an infection, he or she can still become infected with one of the other types. Adenoviruses are unusually stable and can survive for prolonged periods outside the body.
Ongoing research is being conducted in the areas of adenovirus infection and gene therapy with adeno-associated (AAV) vectors. New AAV vectors are being produced and used in clinical trials. These new generation vectors have the potential to be more effective with lower dosage. High-priority areas of research include cystic fibrosis and heart disease.
Adenovirus infections: A number of researchers are focusing on adenoviruses in children because of their increased infection level. One recent study was done in response to recent outbreaks of severe respiratory disease in children.
Lower urinary tract infections (UTIs) are infections of the bladder or the urethra that are usually caused by bacteria. However, a recent study noted an increased incidence of UTIs caused by viruses, including adenoviruses. The study pointed out the need for further research into why adenoviral bladder infections are on the rise.
Gene therapy: Researchers are investigating the use of AAV vectors for the treatment of cancer. Some cancers under current study include rhabdomyosarcoma, an aggressive cancer of skeletal muscles, as well as breast, ovarian, and head and neck cancers. The goal of AAV vector therapy is to inactivate or kill cancer cells. Often AAV vectors are used in combination with traditional forms of cancer treatment, such as chemotherapy and radiation.
AAV vectors are well-suited for gene therapy. They have not been known to cause disease in humans or animals, they do not cause an immune or inflammatory response in moderate dosages, and they remain in the host organism for a long time after introduction. In the future, AAV vectors may be able to deliver toxic substances to cancer cells or to infect and kill cancer cells.
Although it is generally believed that gene therapy with adeno-associated vectors does not trigger an immune response, large vector doses have been reported to do so. The injection of a foreign protein, such as an adenovirus, which has the potential to multiply and possibly mutate within the body, has some risk.
Although gene therapy with AAV is promising, to date it has had limited success in treating diseases such as cancer, cystic fibrosis, and heart disease. Current therapies have not been proven to cure any of these diseases. In some cases, symptoms may have been reduced and survival increased.
Because of the emergence of different and more virulent strains of adenovirus as a result of mutations in the virus, research will continue to focus on developing more effective ways of diagnosing and treating adenovirus-caused infections.
Future gene therapy research with adeno-associated (AAV) vectors has shown potential. Past and current research on AAV vectors has used AAV serotype 2, which is a specific type of virus, as a model. Combined with a better understanding of AAV biology, other types of the virus can be developed in an effort to identify more clinical applications of AAV gene therapies. In addition, these vectors may be more effective and have fewer side effects.
Many AAV vectors are in phase I clinical trials and some, such as those used for the treatment of cystic fibrosis, have progressed to stage II clinical trials. It is hoped that this research will ultimately lead to cures for various diseases.