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Adenoviruses
Human adenoviruses (HAdVs) are a common cause of human disease. Conjunctivitis is a familiar illness associated with the HAdVs, but these viruses also cause upper and lower respiratory disease, pharyngitis, gastroenteritis, and hemorrhagic cystitis. HAdVs can cause severe disease in immunocompromised hosts. Outbreaks of HAdV infection occur in communities and closed populations, notably the military. No currently approved antiviral drugs are highly effective against HAdVs. Vaccines are available for HAdV types 4 and 7 but are used only for military populations.
Etiology
Adenoviruses are nonenveloped viruses with an icosahedral protein capsid. The double-stranded DNA genome is contained within the particle complexed with several viral proteins. Antigenic variability in surface proteins of the virion and genomic sequencing define at least 70 serotypes grouped into seven species. Species differ in their tissue tropism and target organs, causing distinct clinical infections ( Table 289.1 ). HAdVs can be shed from the gastrointestinal tract for prolonged periods and can establish persistent infection of the tonsils and adenoids.
Table 289.1
Adenovirus Types With Associated Infections
| SPECIES | TYPE | PREFERRED SITE OF INFECTION |
|---|---|---|
| A | 12, 18, 31, 61 | Gastrointestinal |
| B | 3, 7, 11, 14, 16, 21, 34, 35, 50, 55, 66 | Respiratory; renal/urinary tract epithelium |
| C | 1, 2, 5, 6, 57 | Respiratory |
| D | 8-10, 13, 15, 17, 19, 20, 22-30, 32, 33, 36-39, 42-49, 51, 53, 54, 56, 58-60, 63-67 | Ocular |
| E | 4 | Respiratory |
| F | 40, 41 | Gastrointestinal |
| G | 52 | Gastrointestinal |
Epidemiology
HAdVs circulate worldwide and cause endemic infections year-round in immunocompetent hosts. Asymptomatic infections are also common. Only about one third of all known HAdV types are associated with clinically apparent disease. The most prevalent types in recent surveillance studies are HAdV types 3, 2, 1, and 5. Epidemics of conjunctivitis (often severe), pharyngitis, and respiratory disease occur, especially in schools and military settings. Outbreaks of febrile respiratory illness caused by HAdV-4 and HAdV-7 are a major source of morbidity in military barracks, with attack rates ranging from 25% to > 90%. The spread of HAdV occurs by respiratory and fecal-oral routes. An important factor in HAdV transmission, especially in epidemics, is the ability of the nonenveloped particle to survive on inanimate objects in the environment. Nosocomial outbreaks have been reported.
Pathogenesis
HAdVs bind to cell surface receptors and trigger internalization by endocytosis. Acidification of the endosome induces conformational changes in the capsid, leading to eventual translocation of the genome to the cell nucleus. Viral messenger RNA transcription and genomic replication occur in the nucleus. Progeny virion particles assemble in the nucleus. Lysis of the cell releases new infectious particles and causes damage to epithelial mucosa, sloughing of cell debris, and inflammation. Host responses to HAdV infection include the recruitment of neutrophils, macrophages, and natural killer cells to the site of infection and the elaboration by those cells of a number of cytokines and chemokines. This host immune response is likely to contribute to the symptoms of HAdV infection, but specific mechanisms of pathogenesis are poorly understood. The strict species specificity of the adenoviruses has precluded the development of an animal model for HAdVs, although recent work with HAdV in a humanized mouse model shows promise. Mouse adenovirus has also been used to study adenovirus pathogenesis using a murine model.
Clinical Manifestations
HAdVs cause a variety of common clinical syndromes in both immunocompetent and immunocompromised hosts. These syndromes are difficult to distinguish reliably from similar illnesses caused by other pathogens, such as respiratory syncytial virus, human metapneumovirus, human rhinovirus, rotavirus, group A streptococcus, and other common viral and bacterial pathogens.
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