Adenoviruses are nonenveloped, icosahedral viruses containing double-stranded linear DNA (Figure 1). They commonly cause diseases such as respiratory tract infections, gastroenteritis, and conjunctivitis. Adenoviruses were first discovered during screenings of throat washings and cultures of adenoids and tonsils, performed in the search for the common cold virus. They are now recognized as a large group of related viruses commonly infecting humans, other mammals, and birds. Over fifty serotypes of human adenoviruses are known, and antibody surveys have shown that most individuals have been infected by several different types by adulthood. Although some human serotypes are highly oncogenic in experimental animals, none have been associated with human malignancies.

Fig1. A. Electron micrograph of an adeno virus virion with fibers. B. Model of adenovirus. C. Crystalline aggregate of adenovirus in the nucleus of a cell.

A. Epidemiology

 and pathogenesis The site of the clinical syndrome caused by an adenovirus infection is generally related to the mode of virus transmission. For example, most adenoviruses are primarily agents of respiratory disease, which are transmitted via the respiratory route. However, most adenoviruses also replicate efficiently and asymptomatically in the intestine, and can be isolated from stool well after respiratory disease symptoms have ended as well as from the stools of healthy persons. Similarly, ocular infections are transmitted by direct inoculation of the eye by virus-contaminated hands, ophthalmologic instruments, or bodies of water in which groups of children swim together.

B. Structure and replication

The adenovirus capsid is composed of hexon capsomers making up the triangular faces of the icosahedron, with a penton capsomer at each of the vertices (see Figure 1). Replication of adenoviruses essentially follows the general model for DNA viruses. Attachment to a host cell receptor occurs via knobs on the tips of the viral fibers, which is followed by entry into the cell by receptor mediated endocytosis. The viral genome is then progressively uncoated while it is transported to the nucleus, where all transcription of viral genes, genome replication, and assembly occurs. Two early viral genes have the same function as the early proteins of the Papovaviridae [that is, inactivating cellular regulatory proteins (including p53 and pRb) that normally prevent progression through the cell cycle]. However, the considerably larger adenovirus genome encodes a number of additional early proteins, including a DNA polymerase and others that affect transcription and replication of the viral genome. The productive cycle kills the host cell, as cellular DNA, RNA, and protein synthesis are all shut off during the course of infection. Release of infectious virus from the cell occurs by slow disintegration of the dying cell.

C. Clinical significance

 Adenoviruses all replicate well in epithelial cells. The observed disease symptoms are related primarily to the killing of these cells, and systemic infections are rare. Most adenovirus infections are asymptomatic, but certain types are more commonly associated with dis ease than others. These diseases can be conveniently grouped into those affecting the: 1) respiratory tract; 2) eye; 3) gastrointestinal (GI) tract; and, less commonly, 4) other tissues, including the urinary tract and heart (Figure 2).

Fig2. Adenovirus infections.

1. Respiratory tract diseases: The most common manifestation of adenovirus infection of infants and young children is acute febrile pharyngitis, characterized by a cough, sore throat, nasal congestion, and fever. Isolated cases may be indistinguishable from other common viral respiratory infections. Some adenovirus types tend additionally to produce conjunctivitis, in which case the syndrome is referred to as pharyngoconjunctival fever. This entity is more prevalent in school-aged children and occurs both sporadically and in outbreaks, often within family groups or in groups using the same swimming facility (“swimming pool conjunctivitis”). The syn drome referred to as acute respiratory disease occurs primarily in epidemics among new military recruits. It is thought to reflect the lowered resistance brought on by exposure to new strains, fatigue, and crowded living conditions, promoting efficient spread of the infection. Lastly, the respiratory syndromes described above may progress to true viral pneumonia, which has a mortality rate of about 10 percent in infants.

2. Ocular diseases: In addition to the conjunctivitis that sometimes accompanies the upper respiratory syndrome described above, a similar follicular conjunctivitis may occur as a separate disease. It is self-limiting and has no permanent sequelae. A more serious infection is epidemic keratoconjunctivitis, which involves the corneal epithelium, and may be followed by corneal opacity lasting several years. The epidemic nature of this disease partly results from transmission via shared towels or ophthalmic solutions, person-to-person contact, and improperly sterilized ophthalmologic instruments.

3. Gastrointestinal diseases: Most human adenoviruses multiply in the GI tract and can be found in stools. However, these are generally asymptomatic infections. Two serotypes have been associated specifically with infantile gastroenteritis. Adenovirus infections have been estimated to account for 5 to 15 percent of all viral diarrheal disease in children.

4. Less common diseases: Several adenovirus serotypes have been associated with an acute, self-limited, hemorrhagic cystitis, which occurs primarily in boys. It is characterized by hematuria, and virus can usually be recovered from the urine. Similarly, adenovirus infection of heart muscle has recently been shown to be one cause of left ventricular dysfunction in both children and adults. In immunocompromised patients, such as those with AIDS, the common respiratory adenovirus infections have a greater risk of proceeding to serious, often fatal, pneumonia. Other disseminated infections leading to a fatal outcome have been reported in patients with a compromised immune system or those immunosuppressed from drug therapy.

 D. Laboratory identification

Isolation of virus for identification is not done on a routine basis but may be desirable in cases of epidemic disease or nosocomial outbreak, especially in the nursery. Identification of the adenovirus serotype can be done by neutralization or hemagglutination inhibition using type-specific antisera. The virus is more commonly detected by direct test of stool specimens by ELISA (enzyme-linked immunosorbent assay).

E. Treatment and prevention

 No antiviral agents are currently available for treating adenovirus infections. Prevention of epidemic respiratory disease by immunization has been used only for protection of the military population. A live, attenuated adenovirus vaccine is used for this purpose that pro duces a good neutralizing antibody response. In 2011, a new vac cine was licensed for use among U.S. military personnel. This vaccine contains live, unattenuated adenovirus types 4 and 7, formulated for oral administration.

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مواضيع ذات صلة

Epstein-Barr Virus

Herpes simplex virus, types 1 and 2

Herpesviridae: Structure and Replication

Human Cowpox

Human Monkeypox

Smallpox virus

Papovaviridae: Subfamily Polyomavirinae

Effects of viral infection on the host cell

Assembly and release of progeny viruses

Clinical Syndromes of Adenovirus

JCPyV and progressive multifocal leukoencephalopathy (PML)

Polyomavirus-associated nephropathy (PVAN)