Adenoviruses

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Chapter 254 Adenoviruses

John V. Williams

Adenoviruses (AdVs) are a common cause of human disease. Conjunctivitis is a familiar illness associated with AdVs, but these viruses also cause upper and lower respiratory disease, pharyngitis, gastroenteritis, and hemorrhagic cystitis. AdVs can cause severe disease in immunocompromised hosts. Outbreaks of AdV occur in communities and close populations, notably the military. No specific antivirals that are highly effective against AdVs are available. Vaccines are available for serotypes 4 and 7 but are used only for military populations.

Etiology

Adenoviruses were first isolated from human adenoidal surgical specimens in 1953. They 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 defines >50 serotypes grouped into seven species. Species differ in their tissue tropism and target organs, causing distinct clinical infections (Table 254-1). AdV can be shed from the gastrointestinal tract for prolonged periods and can establish chronic low-level infection of the tonsils and adenoids.

Table 254-1 ADENOVIRUS SEROTYPES WITH ASSOCIATED INFECTIONS

SPECIES	SEROTYPE	PREFERRED SITE OF INFECTION
A	12, 18, 31	Gastrointestinal
B1	3, 7, 16, 21, 50	Respiratory
B2	11, 14, 34, 35	Renal/urinary tract epithelium
C	1, 2, 5, 6	Respiratory
D	8, 9, 10, 13, 15, 17, 19a, 19p, 20, 22-30, 32, 33, 36, 37, 38, 39, 42-48, 49, 51	Ocular
E	4	Respiratory
F	40, 41	Gastrointestinal

Epidemiology

AdVs circulate worldwide and cause endemic infections year-round in immunocompetent hosts. Asymptomatic infections are also common. Only about one third of all known human AdV serotypes are associated with clinically apparent disease. The most prevalent types in recent surveillance studies are AdVs 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 AdV 4 and AdV 7 are a major source of morbidity in military barracks, with attack rates ranging from 25% to >90%. Spread of AdV occurs by respiratory and fecal-oral routes. An important factor in AdV 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

AdVs 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. AdVs recruit neutrophils, macrophages, and natural killer cells to the site of infection and induce these cells to elaborate a number of cytokines and chemokines. Host immune response thus contributes to the symptoms of AdV infection, but specific mechanisms of pathogenesis are poorly understood.

Clinical Manifestations

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