Related Terms

• AAV vectors, acute respiratory disease, adeno-associated virus vectors, ARD, cancer, cystic fibrosis, gastroenteritis, gene therapy, genetic disease, meningitis, respiratory infection.

Background

• 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.

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.

Risk Factors

• 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.

• 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.

Causes

• Adenovirus infections are caused by adenoviruses, which 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 organism's genetic code.

Signs and Symptoms

• 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.

Diagnosis

• Adenovirus infections can be identified by a number of methods, including antigen detection, blood analysis (serology), virus isolation, and polymerase chain reaction. Antigens are substances recognized by the body as foreign and to which the body produces an immune response. The body's response to an antigen is the production of an antibody to fight the infection. Antigen detection identifies the presence of an adenovirus antigen in the body. Serology is the examination of the blood to determine the presence of antibodies to a virus. Virus isolation is a process whereby a virus from a blood sample is grown in chick embryos to produce many copies of the virus. Polymerase chain reaction is another method of producing multiple copies of a virus in a laboratory.

• Adenovirus typing is often done via hemagglutination inhibition or neutralization (inactivation) with a type-specific antiserum. Hemagglutination inhibition is a test in which a virus-specific antibody is mixed with a patient's blood and virus particles. The degree to which the blood cells clump together (agglutinate) indicates the level of an individual's immune response to the virus. An antiserum is a solution that contains substances that fight against infection. The presence of an adenovirus in an individual does not indicate an active infection. An adenovirus can be excreted for prolonged periods, even months to years, after acquiring the virus.

Complications

• 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.

• Although most adenovirus infections are minor, some can be serious. Even minor infections can cause missed work or school and the treatment of adenoviruses increases healthcare costs.

• Despite the fact that they are not ill, carriers of adenoviruses have the ability to spread the organism for months and even years. These individuals thus present a threat to those susceptible to developing adenovirus infections.

Treatment

• General: In contrast to antibiotics for a bacterial infection, virus-specific treatment for an adenovirus infection is currently unknown. Vaccines have only been developed for acute respiratory disease (ARD) in military recruits. Most adenovirus infections are not severe and can be managed by treating symptoms, getting rest, and assuring adequate fluid intake to avoid dehydration.

• New adenovirus-caused illnesses are now appearing. These viruses are mutations of previous forms of the virus. They produce typical adenovirus illnesses and can infect individuals who are immune to previous forms of the virus. Treatment options beyond supportive care, such as hydration, rest, and medication for relief of symptoms, are limited.

• Gene therapy: Gene therapy may help in the treatment of a number of diseases. It is a process whereby 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, a normally functioning gene can be injected to replace the defective one.

• Adenoviruses can be used as vectors of genetic material into a cell. When used in this capacity, they are known as adeno-associated (AAV) vectors. This genetic material can correct genetic disorders, such as cystic fibrosis. AAV vectors can also aid in the treatment of nongenetic diseases, such as heart disease, by restoring the function of damaged cells.

Integrative Therapies

• Note: Currently there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of adenovirus infections. The therapies below have been studied for their effect on various viral infections, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies.

• Unclear or conflicting scientific evidence:

• Alizarin: Limited available evidence suggests that alizarin may improve various herpes infections. Additional study is needed before a firm recommendation can be made. Avoid if allergic or hypersensitive to alizarin or any plants in the Rubiaceae family. Alizarin may be toxic and should not be handled for long periods of time, rubbed in the eyes, or eaten. Avoid if pregnant or breastfeeding.

• Astragalus: Astragalus products are derived from the roots of Astragalus membranaceus or related species, which are native to China. In traditional Chinese medicine, astragalus is commonly found in mixtures with other herbs, and is used in the treatment of numerous ailments, including heart, liver, and kidney diseases, as well as cancer, viral infections, and immune system disorders. Anti-viral activity has been reported with the use of astragalus in laboratory and animal studies. Limited human research has examined the use of astragalus for viral infections in the lung, heart (pericarditis, myocarditis, endocarditis), liver (hepatitis B and C), cervix (papilloma virus), and in HIV disease. Studies have included combinations of astragalus with the drug interferon, or as a part of herbal mixtures. However, most studies have been small and poorly designed. Due to a lack of well-designed research, firm conclusions cannot be drawn.

• Avoid if allergic to astragalus, peas, or any related plants, or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant or autoimmune diseases (like HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.

• Blessed thistle: Blessed thistle leaves, stems, and flowers have traditionally been used in "bitter" tonic drinks and in other preparations taken by mouth to enhance appetite and digestion. Evidence of activity of blessed thistle against herpes viruses, influenza, or poliovirus is currently lacking in available preliminary research. Effects of blessed thistle (or chemicals in blessed thistle called lignans) against HIV are not clear. Human research of blessed thistle as a treatment for viral infections is lacking.

• Avoid if allergic to blessed thistle, mugwort, bitter weed, blanket flower, chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed, Echinacea or any plants of the Asteraceae or Compositae families. Use cautiously with peptic ulcer disease. Avoid with a history of bleeding diseases or gastroesophageal reflux disease (GERD), or if taking drugs for blood thinning, stroke, stomach diseases, or to control stomach acid. Avoid if pregnant or breastfeeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures.

• Cranberry: Cranberry is popular as a food, and is often consumed as relish, sauce, jam, juice, or dried berries. Limited laboratory research has examined the antiviral activity of cranberry. Reliable human studies supporting the use of cranberry in this area are currently lacking. Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium genus. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.

• Focusing: Early research showed that increased experiential involvement (an indication of focusing taking place) did not have an effect on antibody titers to Epstein-Barr virus. More studies in the area of immune function and antibody production are required before a recommendation can be made in this area.

• Green tea: Preliminary research suggests that green tea decreases viral load in carriers of the HTLV-1 virus. Additional well-designed controlled research is needed before a recommendation can be made for or against use of green tea in the treatment of HTLV-1 carriers. Avoid if allergic or hypersensitive to caffeine or tannin. Use cautiously with diabetes or liver disease.

• Sorrel: Historically, sorrel has been used as a salad green, spring tonic, diarrhea remedy, weak diuretic, and soothing agent for irritated nasal passages. Sorrel has been used with other herbs to treat bronchitis and sinus conditions in Germany since the 1930s. There is currently a lack of well-conducted published studies that demonstrate antiviral or antibacterial activity of sorrel. In available laboratory study, sorrel did not demonstrate activity against herpes simplex virus-1, herpes simplex virus-2, HIV, B. subtilis, E. coli, Proteus morganii, Pseudomonas aeruginosa, P. vulgaris, Serratia marcescens, or Staphylococcus aureus.

• Avoid with a known allergy to sorrel. Avoid large doses of sorrel because there have been reports of toxicity and death, possibly due to oxalates found in sorrel. Tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. High alcohol sorrel formulations may also cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.

• Turmeric: The rhizome (root) of turmeric (Curcuma longa Linn.) has long been used in traditional Asian medicine to treat gastrointestinal upset, arthritic pain, and "low energy." Evidence suggests that turmeric may help treat viral infections. However, there is currently not enough human evidence in this area. Well-designed trials are needed to determine if these claims are true.

• Avoid if allergic or hypersensitive to turmeric, curcumin, yellow food colorings, or plants belonging to the Zingiberaceae (ginger) family. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, diabetes, hypoglycemia, or gallstones. Use cautiously with blood-thinners, such as warfarin (like Coumadin®), and blood sugar-altering medications. Avoid in medicinal amounts if pregnant or breastfeeding. Turmeric should be stopped prior to scheduled surgery.

• Vitamin A: The role of vitamin A in the prevention, transmission, or treatment of HIV is controversial and not well established. A clear conclusion cannot be formed based on the available scientific research. Vitamin A supplementation has also been suggested to help prevent NoV infection in children and reduce the symptoms associated with NoV infections. Additional research is needed in this area.

Prevention

• Transmission of adenoviruses may occur by direct contact, fecal-oral transmission, and sometimes via contact with infected water. Direct contact transmission is preventable by using good hygiene practices, such as hand washing. Fecal-oral (hand to mouth) transmission is preventable by hand washing after using the restroom or changing an infant's diapers. Waterborne transmission is preventable by maintaining appropriate chlorine levels in swimming pools and by not sharing personal items such as towels.

• Some individuals are healthy carriers of adenoviruses, meaning that they are "colonized" with the virus in their tonsils, adenoids, or intestines. These individuals can shed the virus for months or even years and may therefore be the source of illness for others.

Research

• 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.

Future Research

• 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.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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