Adenoviruses. Structure and Physical/Chemical Properties

Introduction. Adenoviruses cause a wide range of human illnesses. The most common are gastroenteritis, respiratory infections, and eye infections, especially in children and young adults. They are the second most common cause of gas­troenteritis in children and are a major source of serious respiratory infections among military recruits.

Increasing evidence in recent years also suggests that infection with adenovirus type 36 may be associated with obesity in humans. While mortality from adenovirus infections is usually low, there is a serious risk of death among the immunocompromised (e.g., transplant patients, AIDS patients), with rates approaching 60% of those infected.

Human adenoviruses belong to the family Adenoviridae. The family classification is subdivided into the Mast-adenovirus and Aviadenovirus genera. The Mastadenovirus genus includes all of the species infecting humans as well as the simian, murine, bovine, equine, porcine, ovine, and canine species and those infecting opossums. The Aviade­novirus genus only includes viruses that infect avian spe­cies. In general, the natural host ranges of adenoviruses are confined to one species or closely related species.

Currently, there are 51 identifiable human adenovirus serotypes. These are divided into six subgroups (A—F) and four hemagglutination groups (I-IV). Each serotype is distinguished by its resistance to neutralization by anti­sera to other known adenovirus serotypes. Serotypes are designated based on their oncogenicity and hemaggluti­nation groups are based on their ability to agglutinate rhesus monkey and rat erythrocytes. Table 1 outlines the current classification scheme for human adenovirus serotypes.

Table 1. Human adenovirus serotype classification

Structure and Physical/Chemical Properties.Adenoviruses have a nonenveloped, icosahedral virion that consists of a core containing linear, double-stranded DNA (26-45 kbp) enclosed by a capsid. The capsid is composed of 252 capsomers, 240 of which are hexons and 12 of which are pentons. Each penton projects a single fiber that varies in length for each serotype, an exception being the enteric adenovirus (EAds) pentons (serotypes 40 and 41) that project two fibers. Adenoviruses are approximately 70 to 100 nm in diameter.

Adenoviruses may survive extended periods of time outside host cells. They are stable in the presence of many physical and chemical agents, as well as adverse pH con­ditions. For example, adenoviruses are resistant to lipid solvents due to the lack of lipids within their structure. Infectivity is optimal between pH 6.5 and 7.4; however, the viruses can withstand pH ranges between 5.0 and 9.0. Adenoviruses are heat resistant (particularly type 4) and may remain infectious after freezing.

Illnesses.Routes of infection include the mouth, nasopharynx, and the ocular conjunctiva. Transmission is largely person to person, probably by way of aerosols and fomites. Of the 51 known human serotypes, only one-third are associated with human disease (Table 2) while the remainder appear to largely cause ion asymptomatic infections.

Table 2. Common illnesses associated with human adenoviruses

Adenoviruses are associated with a variety of clini­cal illnesses involving almost every human organ system. Illnesses include upper (pharyngitis and tonsillitis) and lower (bronchitis, bronchiolitis, and pneumonia) respira­tory illnesses, conjunctivitis, cystitis, and gastroenteritis. Less frequently, the virus can become systemic and affect the bladder, liver, pancreas, myocardium, or central nervous system. Several studies have found that the enteric adenoviruses are second only to rotaviruses as the causative agents of acute gastroenteritis in infants and young children.

Most illnesses caused by adenoviruses are acute and self-limiting. Although the symptomatic phase may be short, all adenoviruses can remain in the gastrointestinal tract and continue to be excreted for an extended period of time. Species within subgenera C may continue to be excreted for months or even years after disease symptoms have resolved. Adenoviruses can remain latent in the body (in tonsils, lymphocytes, and adenoidal tissues) for years and be reactivated under certain conditions, such as a change in immune status. The long-term effect of such a latent infection is unknown.

Adenovirus infections may be accompanied by diar­rhea, though the virus can be excreted even if diarrhea is not present. A large proportion of infections caused by subgenera A and D tend to be asymptomatic, whereas the species within subgenera B and E tend to result in a higher rate of symptomatic respiratory illnesses. Immunity is serotype-specific. The presence of preexisting antibodies resulting from a previous infection is usually protective and, in such cases, symptomatic infection is rare.

It is often difficult to confidently link adenoviruses to specific illnesses because asymptomatic, healthy people can shed viruses. Occurrence studies comparing infection in healthy and ill people have found up to 20% of asymp­tomatically infected persons can shed adenovirus. Adeno­viruses cause 5% of all infectious illnesses in infants and 3% in children aged 2 to 4 years.

Certain species of adenoviruses are oncogenic (from subgenera A and B), yet only when a human virus is introduced into an animal model. Investigations into pos­sible human cancer effects through searches for tumor antigens and DNA sequences have been negative.