Adenoviruses (Salem Health: Cancer)
Cancers treated: Breast, colorectal, head and neck, liver, and prostate cancers
Delivery routes: Injection
How these agents work: Adenoviruses are nonenveloped, or naked, viruses, meaning that they lack a lipid and protein outer covering. Counterintuitively, viruses without this outer covering are better able to withstand environmental stressors such as an acidic environment, drying, and heat and therefore may live longer outside a host cell. Most adenoviruses cause respiratory illnesses, conjunctivitis (pinkeye), or gastroenteritis and are transmitted via respiratory droplets or through fecal-oral transmission.
Adenoviruses are well suited to gene therapy because of their environmental robustness, the ease of manipulating the adenovirus genome, and their ability to infect a number of different kinds of tissue. The DNA inside the adenovirus may one day be altered to encode up to forty genes.
In cancer therapy, adenoviruses are first inactivated to make them incapable of causing infection once inside the body. When injected into cancer cells, the virus can cause cell death or tumor suppression by producing toxic proteins, flagging cells for destruction by the immune system, breaking the cell apart (cell lysis), or activating genes that will cause the cell to die (apoptosis) or stop replicating.
To gain access to host cells, adenoviruses attach to a receptor on...
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Causes and Symptoms (Magill’s Medical Guide, Sixth Edition)
Adenoviruses derive their name from their family name of Adenoviridae, which can be further classified biologically according to several genera that can cause infections in a wide range of vertebrates, including humans and birds. Birds are commonly infected by the Aviadenovirus genus and the Siadenovirus genus, with examples including the Fowl adenovirus A of the Aviadenovirus genus and the Turkey adenovirus B of the Siadenovirus genus. Humans can become infected by any of the subgroups labeled A through F of the Mastadenovirus genus. These six subgroups of Mastadenovirus consist of more than forty-nine human adenovirus serotypes. Members of subgroups C, D, E, and F can cause the symptoms of bronchitis, common cold syndrome, conjunctivitis, croup, cystitis, diarrhea, gastroenteritis, pneumonia, and skin rashes. While they do not cause cancer, adenovirus members of subgroups A and B have been shown to cause tumor growth in mice.
Exposure to the virus in insufficiently chlorinated swimming pools and drinking water can lead primarily to conjunctivitis, diarrhea, gastroenteritis, and skin rashes, while direct contact or fecal-oral transmission can lead to these symptoms as well as infections that act primarily on the respiratory system, such as the common cold, bronchitis, and pneumonia. Poorly disinfected surfaces in public areas or crowded...
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Treatment and Therapy (Magill’s Medical Guide, Sixth Edition)
Although outbreaks of adenovirus infection occur most often in winter, spring, and early summer, it is possible for infection to occur anytime during the year. Some adenoviruses are actually endemic to some parts of the world with especially unsanitary conditions. Young children are infected by adenoviruses with the greatest frequency, and most people have been infected by at least one adenovirus by the age of ten. Generally, the symptoms are treated, but no treatment specifically targets the adenovirus itself. Unfortunately, some adenoviruses can survive for days outside of the body because of their stability to both acidic and basic conditions. Therefore, the best treatment continues to be prevention through frequent hand washing and avoidance of the fecal-oral transmission that can occur with poor quality drinking water or direct contact with the water of small lakes, as well as transmission via insufficiently chlorinated swimming pools.
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
As technology has evolved, more details regarding the many different types of adenoviruses have become available. Adenoviruses were first isolated by researchers in 1953 as a result of concern for widespread respiratory infections. Further testing in 1962 revealed that mice developed tumors after exposure to some adenoviruses. In addition to the developments of X-ray crystallography and microscopy instrumentation, advances in genetic techniques have allowed more in-depth investigation and identification of additional adenoviruses. For example, another subgroup of adenovirus has been implicated as a cause of obesity in some humans. Diagnosis was assisted by genetic techniques including polymerase chain reaction (PCR) assays, virus isolation, and adenovirus typing that was not available to investigators decades ago. Thus, further advances in treatment are expected.
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
American Academy of Pediatrics. “Adenovirus Infections.” In Red Book: Report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, Ill.: Author, 1997.
Foy, H. M. “Adenoviruses.” In Viral Infections in Humans: Epidemiology and Control. 4th ed. New York: Plenum, 1997.
Gray, G. C. “Adenovirus Transmission—Worthy of Our Attention.” Journal of Infectious Diseases 194 (July, 2006): 871-873.
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Adenoviruses (World of Microbiology and Immunology)
Adenoviruses are viruses which have twenty sides. As such they are called icosahedrons. The outer surface, the capsid, is made of particles of a protein. The protein is arranged in groups of six (hexagons) except at the twenty points where the sides meet (each is called an apex), where the particles are in a pentagon arrangement. A so-called penton fibre, which resembles a stick with a ball at the end, protrudes from each apex.
Adenoviruses contain deoxyribonucleic acid (DNA) as their genetic material. The DNA encodes 20 to 30 proteins, 15 of which are proteins that form the structure of the virus particle. Similar to other viruses, adenoviruses invade a host cell and use the host genetic machinery to manufacture new virus particles. The new viruses are released from the host cell.
Children suffer from adenovirus infections much more so than adults.
The viruses of this group infect the membranes that line the respiratory tract, the eyes, the intestines, and the urinary tract. The adenoviruses that infect humans usually cause mild maladies, including respiratory and intestinal illnesses and conjunctivitis (an inflammation of eye membrane, which is also commonly called "pink eye"). A more severe eye malady called keratoconjunctivitis can more widely infect the eye. The eye infections are very contagious and are typically a source of transmission of adenovirus from one person to another. Children can also develop a sore throat, runny nose, cough and flu-like illness. Bronchitis, an inflammation of the membranes lining the air passages in the lungs, can also result from adenovirus infection, as can an inflammation of the stomach called gastroenteritis. Urinary tract infections can cause pain and burning upon urination and blood in the urine. In dogs, adenovirus type 2 causes what is known as kennel cough. But curiously, the virus also protects dogs against hepatitis.
In the setting of the laboratory, some of the human strains of adenovirus can transform cells being grown in cell culture. Transformed cells are altered in their regulation of growth, such that the unrestricted growth characteristic of cancers occurs.
Adenoviruses have been known since the mid-1950s. They were first isolated from infected tonsils and adenoidal tissue in 1953. Within the next several years they had been obtained from cells involved in respiratory infections. In 1956, the multiple antigenic forms of the virus that had been discovered were classified as adenovirus. Then, in 1962, laboratory studies demonstrated that an adenovirus caused tumors in
More recently, the basis of the tumor-inducing activity has been unraveled. Genes that are active early in the replication cycle of adenovirus produce proteins that interfere with host proteins that are known as anti-oncogenes. Normally, the anti-oncogen proteins are responsive to cell growth, and so act as a signal to the cell to halt growth. By disrupting the anti-oncogene proteins, this stop signal is eliminated, resulting in the continued and uncontrolled growth of the cell. A tumor is produced. Thus, adenoviruses have become important as one of the central triggers of cancer development.
Such cancers may be a by-product of adenovirus infections. These infections are not by themselves serious. Most tend to appear and run their course within a few weeks. The infections are fairly common. For example, most children will have antibodies to at least four types of adenovirus. Adenovirus gains entry through a break in the skin or are inhaled. The stick-and-ball appearing penton fibers may have a role in the attachment of the virus particle to a protein on the surface of the host epithelial cell.
Adenovirus infections have contributed to the spread of bacterial antibiotic resistance because of the overuse of antibiotics. The flu-like symptoms of some adenovirus infections can lead to the prescribing of antibiotics as a treatment. However, antibiotics are ineffective against viruses. But the circulating antibiotic can provide selective pressure on the development of resistant in bacterial populations.
See also Bacterial adaptation; Transformation